Mixed Topics

Adults with atopic dermatitis are at sharply increased risk for a broad array of comorbid dermatologic conditions. Also today, flu season is showing signs of slowing, BMI changes in adolescence is linked to cancer risk later in life, and does reduced degradation of insulin by the liver cause type 2 diabetes.
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Adults with atopic dermatitis are at sharply increased risk for a broad array of comorbid dermatologic conditions. Also today, flu season is showing signs of slowing, BMI changes in adolescence is linked to cancer risk later in life, and does reduced degradation of insulin by the liver cause type 2 diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Adults with atopic dermatitis are at sharply increased risk for a broad array of comorbid dermatologic conditions. Also today, flu season is showing signs of slowing, BMI changes in adolescence is linked to cancer risk later in life, and does reduced degradation of insulin by the liver cause type 2 diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Ray Barfied, MD, is professor of pediatrics and of Christian philosophy at Duke University. In part I of the conversation, Dr. Barfield and MDedge host Nick Andrews discussed physician burnout and Dr. Barfield’s journey back to medicine. In this episode, Dr. Barfield and Nick discuss philosophy and science.

You can listen to part I of this conversation here:
Apple Podcasts
Google Podcasts
Spotify
 

Ray Barfied, MD, is professor of pediatrics and of Christian philosophy at Duke University. In part I of the conversation, Dr. Barfield and MDedge host Nick Andrews discussed physician burnout and Dr. Barfield’s journey back to medicine. In this episode, Dr. Barfield and Nick discuss philosophy and science.

You can listen to part I of this conversation here:
Apple Podcasts
Google Podcasts
Spotify
 

Ray Barfied, MD, is professor of pediatrics and of Christian philosophy at Duke University. In part I of the conversation, Dr. Barfield and MDedge host Nick Andrews discussed physician burnout and Dr. Barfield’s journey back to medicine. In this episode, Dr. Barfield and Nick discuss philosophy and science.

You can listen to part I of this conversation here:
Apple Podcasts
Google Podcasts
Spotify
 

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD also is an independent risk factor for cardiovascular disease, type 2 diabetes mellitus (T2DM), chronic kidney disease, cirrhosis, liver cancer, and all-cause mortality.^1-3 As the leading cause of liver disease in the US and globally, NAFLD is strongly associated with obesity and metabolic syndrome, with the rising prevalence of NAFLD closely mirroring the epidemic of obesity and T2DM.^4,5 The unrelenting increase of NAFLD prevalence has led to a significant rise in associated health care and economic burdens, compounded by the boom in childhood obesity and an aging population. In this review, we will discuss the epidemiology and economic burden of NAFLD in the US and how it affects veteran health.

NAFLD Definition

NAFLD is defined as the presence of > 5% of hepatic steatosis in the absence of excessive alcohol use, steatosis-inducing medication, or other concurrent chronic liver diseases. 

Compared with patients with NAFL, patients with NASH are at a much higher risk of developing fibrosis (scarring of the liver) and cirrhosis (significant scarring with distorted liver architecture). Patients with either NAFL or NASH, with or without advanced fibrosis, also can develop hepatocellular carcinoma (HCC). Severity of liver fibrosis (ie, fibrosis stage) is the most important predictor of liver-associated mortality and all-cause mortality; those with significant fibrosis (≥ F2 stage of fibrosis) are more likely to die of liver disease or to undergo a liver transplant compared with those with earlier stages of disease (ie, stages 0 to F1). Those with advanced scarring or cirrhosis (≥ F3 stage of fibrosis) exhibit an even higher risk of death or liver transplantation.⁶

NAFLD is a slow and often progressive disease. Time to progression between each stage of fibrosis is about 7 years; however, there has been a documented subset of patients with rapid progression to advanced fibrosis.⁷ The risk factors associated with this increased risk of fibrosis progression remain poorly understood.

Prevalence

The prevalence of NAFLD in the US is about 24% to 26%—about 85 million Americans. Up to 20% to 30% of these cases (about 17-25 million Americans) are thought to have NASH (Figure 2). 

Although liver biopsy remains the current gold standard for diagnosis and histopathologic staging of NAFLD, alternatives to liver biopsy include elastography techniques (ie, transient elastography using Fibroscan[Paris, France], shear wave elastography using Supersonic Image Aixplorer [Weston, FL], and magnetic resonance elastography), magnetic resonance spectroscopy, liver enzymes, and noninvasive simple and complex (serologic) scoring systems such as the Fatty Liver Index. Among these, liver enzymes and serologic scores are most likely to underestimate NAFLD disease burden. Transient elastographyis widely used because the test is easy to perform, noninvasive, and reliably estimates the degree of liver fibrosis in patients with NAFLD by measuring the speed of a mechanically induced shear wave using pulse-echo ultrasonic acquisitions in a much larger portion of the tissue (about 100 times more than a liver biopsy core). Transient elastography also can objectively quantify the amount of liver fat by measuring a 3.5 MHz ultrasound coefficient of attenuation or controlled attenuation parameter (CAP). This correlates with the degree of liver fat, and a higher CAP level reflects a greater degree of steatosis.

The largest study of US veterans utilized abnormal (ie, elevated) liver enzymes as the diagnostic criteria and reviewed nearly 10 million veterans who were followed between 2003 and 2011. Investigators reported a NAFLD prevalence of 13.6% in this population and noted an overall increase in NAFLD prevalence from 6.3% in 2003 to 17.6% in 2011, which highlights the continued growth in NAFLD clinical burden.¹⁰ This study, however, is likely to have underestimated the prevalence of NAFLD among veterans because liver enzymes are often normal among those with NAFLD (ie, low sensitivity), and the prevalence of obesity and T2DM are significantly higher in the veteran population vs the general population.

Incidence

There are limited studies on NAFLD incidence. The largest study of US veterans to date used liver enzymes as its diagnostic criteria and reported an annual NAFLD incidence of 2 to 3 per 100 persons (over 9 years from 2003 to 2011).¹⁰ There are a few studies from Asia and Europe, and a recent pooled meta-analysis of these studies reported the incidence of NAFLD in Asia to be 52.3 per 1,000 person-years; the incidence in Western countries was 28 per 1,000 person-years.⁵ These variances may be explained, in part, to disparities in race/background. For example, Hispanics and South Asians (ie, people from Bangladesh, India, or Pakistan) are at higher risk for NAFLD/NASH.¹¹ These findings reinforce the need for further studies to better estimate the true incidence of NAFLD among veterans.

Chronic Liver Disease, Cirrhosis, and Hepatocellular Carcinoma

The prevalence of NASH cirrhosis also has been evaluated using serologic scores, such as aspartate aminotransferase to platelet ratio index (APRI). The National Health and Nutrition Examination Survey (NHANES) database was reviewed, and data for adults in 2 separate periods were analyzed (1999-2002 and 2009-2012) and the prevalence of NASH cirrhosis was noted to have increased 2.5-fold over the period (0.072% vs 0.178%, P < .05).¹¹ Based on data from the HealthCore Integrated Research Database from 2006 to 2014, about 15% of cirrhosis cases were attributed to NAFLD, and about 24% each were attributed to hepatitis C virus (HCV) and alcoholic liver disease.¹² A review of about 60,000 veterans with cirrhosis between 2001 and 2013 revealed a prevalence of NAFLD-related cirrhosis of about 15%, while 48% were attributed to HCV.¹³ In contrast to the continued increase in NAFLD prevalence, the number of patients with HCV-associated liver disease has been in gradual decline since the advent of direct acting antiviral medications in 2011.¹²

Based on data from the United Network for Organ Sharing (UNOS), the number of patients awaiting liver transplant due to NAFLD nearly tripled from 2004 to 2013, and in 2013 NAFLD became the second leading disease among waitlisted patients for liver transplantation.¹⁴ Dynamic Markov modeling predicts that cases of decompensated NASH cirrhosis (ie, liver failure) will rise by 161%, from about 144,000 to 376,000 cases over the next 15 years.⁸ These projections predict that NAFLD will overtake HCV as the leading cause of chronic liver disease among patients awaiting a liver transplant and will pose a significant clinical and economic burden in the coming years.

Aside from cirrhosis due to NAFLD, NAFLD-related HCC has been on the rise and has overtaken HCV-related HCC. UNOS data from 2003 to 2015 have shown a 2-fold decline in liver transplantation for HCV-associated HCC; however, the same period saw a 10-fold increase in liver transplantation for NAFLD-associated HCC.^15,16 This trend in NAFLD-related HCC is expected to grow from 5,000 to 6,000 cases in 2005 to 45,000 cases by 2025.⁹ More surprisingly, studies from the US veteran population have reported that patients with NAFLD-related HCC are less likely to have cirrhosis compared with patients with HCV- or alcohol-related HCC.¹⁷ Among all US veterans who developed HCC in the absence of cirrhosis between 2005 and 2010, NAFLD and metabolic syndrome seemed to be the leading risk factors for development of HCC.¹⁸ These trends raise concern for the rise in noncirrhotic HCC in the NAFLD population and highlight the need to improve current screening guidelines for this subset of patients.

Economic Burden

With such a heavy clinical burden and a projected increase in volume over the next decade, NAFLD is expected to have a similarly exponential impact on the economic burden. A review of 976 Medicare beneficiaries with NAFLD who were hospitalized from January 1, 2010 to December 31, 2010, noted a median annual total payment of about $11,000, with significantly lower payment for patients without cirrhosis compared with those with cirrhosis ($10,146 vs $18,804, P < .01).¹⁹ Another review of 29,528 Medicare beneficiaries with NAFLD who sought outpatient care between 2005 and 2010 saw a rise in mean yearly charges in 2005 of $2,624 ± 3,308 to $3,608 ± 5,132 in 2010 (P < .05).²⁰

To place these costs in perspective, Allen and colleagues reviewed a large national claims database of individuals enrolled with private and Medicare advantage health plans.²¹ Comparing patients with NAFLD with a control matched group with similar metabolic comorbidities the study revealed annual median outpatient care costs of $5,363 for the patients with NAFLD with Medicare advantage plans, which was significantly higher than $4,111 for the control group. Projection models based on similar Medicare beneficiaries estimate a rise in annual US economic burden to $103 billion from direct medical care costs alone and another $188 billion in societal costs related to NAFLD.²² New NASH/antifibrotic therapies are being evaluated in clinical trials and are expected to lead to even higher costs. Given the similarities in the trends of NAFLD prevalence between veterans and the general population, it is anticipated that a similar growth and burden in health care utilization cost will affect the VHA.

Association With Other Chronic Medical Conditions

NAFLD is closely associated with metabolic syndrome (Figure 3). Concurrent diagnosis of NAFLD in patients with existing T2DM is associated with poor glycemic control, progressive diabetic retinopathy, diabetic nephropathy, increased risk of cardiovascular complications, and a 2-fold increase in all-cause mortality.^1-3 

Similar associations have been described between NAFLD and other metabolic conditions such as obesity, hypertension, hypothyroidism, polycystic ovarian syndrome, and chronic kidney disease.³¹ Identifying patients with NAFLD may help with screening for the above metabolic diseases because patients with NAFLD (by comparison with patients with non-NAFLD) are at higher risk for diabetic, cardiovascular, and pulmonary complications and may warrant a more intensive treatment approach.

Conclusion

A leading cause of chronic liver disease and cirrhosis in the US, NAFLD is independently associated with metabolic syndrome and all-cause mortality. The number of veterans with NAFLD is expected to grow significantly over the coming years given the ongoing epidemic of adult and childhood obesity and T2DM. It is associated with many other medical conditions, including cardiovascular disease and complications, incident metabolic diseases, and may progress to liver cirrhosis and cirrhosis associated complications like HCC and liver failure. The current lack of any approved drug treatment for NASH/fibrosis and the shortage of organs for liver transplant emphasize the need for comprehensive primary prevention measures to reduce the future health and economic costs associated with NAFLD.

There is a growing need to address the epidemic of metabolic syndrome, as heralded by the World Health Organization in its 2013 global action plan. To address this multifaceted disease, initial approach should be to improve NAFLD education among veterans, beginning with the primary care teams and extending to specialty care, including hepatologists. Future steps also should include the development of a comprehensive metabolic/NAFLD clinic in all US Department of Veterans Affairs medical centers that integrates multidisciplinary care, point-of-care evaluation (eg, elastography staging of disease), and access to clinical trials, and have NAFLD care/outcome as a key performance target for all providers.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD also is an independent risk factor for cardiovascular disease, type 2 diabetes mellitus (T2DM), chronic kidney disease, cirrhosis, liver cancer, and all-cause mortality.^1-3 As the leading cause of liver disease in the US and globally, NAFLD is strongly associated with obesity and metabolic syndrome, with the rising prevalence of NAFLD closely mirroring the epidemic of obesity and T2DM.^4,5 The unrelenting increase of NAFLD prevalence has led to a significant rise in associated health care and economic burdens, compounded by the boom in childhood obesity and an aging population. In this review, we will discuss the epidemiology and economic burden of NAFLD in the US and how it affects veteran health.

NAFLD Definition

NAFLD is defined as the presence of > 5% of hepatic steatosis in the absence of excessive alcohol use, steatosis-inducing medication, or other concurrent chronic liver diseases. 

Compared with patients with NAFL, patients with NASH are at a much higher risk of developing fibrosis (scarring of the liver) and cirrhosis (significant scarring with distorted liver architecture). Patients with either NAFL or NASH, with or without advanced fibrosis, also can develop hepatocellular carcinoma (HCC). Severity of liver fibrosis (ie, fibrosis stage) is the most important predictor of liver-associated mortality and all-cause mortality; those with significant fibrosis (≥ F2 stage of fibrosis) are more likely to die of liver disease or to undergo a liver transplant compared with those with earlier stages of disease (ie, stages 0 to F1). Those with advanced scarring or cirrhosis (≥ F3 stage of fibrosis) exhibit an even higher risk of death or liver transplantation.⁶

NAFLD is a slow and often progressive disease. Time to progression between each stage of fibrosis is about 7 years; however, there has been a documented subset of patients with rapid progression to advanced fibrosis.⁷ The risk factors associated with this increased risk of fibrosis progression remain poorly understood.

Prevalence

The prevalence of NAFLD in the US is about 24% to 26%—about 85 million Americans. Up to 20% to 30% of these cases (about 17-25 million Americans) are thought to have NASH (Figure 2). 

Although liver biopsy remains the current gold standard for diagnosis and histopathologic staging of NAFLD, alternatives to liver biopsy include elastography techniques (ie, transient elastography using Fibroscan[Paris, France], shear wave elastography using Supersonic Image Aixplorer [Weston, FL], and magnetic resonance elastography), magnetic resonance spectroscopy, liver enzymes, and noninvasive simple and complex (serologic) scoring systems such as the Fatty Liver Index. Among these, liver enzymes and serologic scores are most likely to underestimate NAFLD disease burden. Transient elastographyis widely used because the test is easy to perform, noninvasive, and reliably estimates the degree of liver fibrosis in patients with NAFLD by measuring the speed of a mechanically induced shear wave using pulse-echo ultrasonic acquisitions in a much larger portion of the tissue (about 100 times more than a liver biopsy core). Transient elastography also can objectively quantify the amount of liver fat by measuring a 3.5 MHz ultrasound coefficient of attenuation or controlled attenuation parameter (CAP). This correlates with the degree of liver fat, and a higher CAP level reflects a greater degree of steatosis.

The largest study of US veterans utilized abnormal (ie, elevated) liver enzymes as the diagnostic criteria and reviewed nearly 10 million veterans who were followed between 2003 and 2011. Investigators reported a NAFLD prevalence of 13.6% in this population and noted an overall increase in NAFLD prevalence from 6.3% in 2003 to 17.6% in 2011, which highlights the continued growth in NAFLD clinical burden.¹⁰ This study, however, is likely to have underestimated the prevalence of NAFLD among veterans because liver enzymes are often normal among those with NAFLD (ie, low sensitivity), and the prevalence of obesity and T2DM are significantly higher in the veteran population vs the general population.

Incidence

There are limited studies on NAFLD incidence. The largest study of US veterans to date used liver enzymes as its diagnostic criteria and reported an annual NAFLD incidence of 2 to 3 per 100 persons (over 9 years from 2003 to 2011).¹⁰ There are a few studies from Asia and Europe, and a recent pooled meta-analysis of these studies reported the incidence of NAFLD in Asia to be 52.3 per 1,000 person-years; the incidence in Western countries was 28 per 1,000 person-years.⁵ These variances may be explained, in part, to disparities in race/background. For example, Hispanics and South Asians (ie, people from Bangladesh, India, or Pakistan) are at higher risk for NAFLD/NASH.¹¹ These findings reinforce the need for further studies to better estimate the true incidence of NAFLD among veterans.

Chronic Liver Disease, Cirrhosis, and Hepatocellular Carcinoma

The prevalence of NASH cirrhosis also has been evaluated using serologic scores, such as aspartate aminotransferase to platelet ratio index (APRI). The National Health and Nutrition Examination Survey (NHANES) database was reviewed, and data for adults in 2 separate periods were analyzed (1999-2002 and 2009-2012) and the prevalence of NASH cirrhosis was noted to have increased 2.5-fold over the period (0.072% vs 0.178%, P < .05).¹¹ Based on data from the HealthCore Integrated Research Database from 2006 to 2014, about 15% of cirrhosis cases were attributed to NAFLD, and about 24% each were attributed to hepatitis C virus (HCV) and alcoholic liver disease.¹² A review of about 60,000 veterans with cirrhosis between 2001 and 2013 revealed a prevalence of NAFLD-related cirrhosis of about 15%, while 48% were attributed to HCV.¹³ In contrast to the continued increase in NAFLD prevalence, the number of patients with HCV-associated liver disease has been in gradual decline since the advent of direct acting antiviral medications in 2011.¹²

Based on data from the United Network for Organ Sharing (UNOS), the number of patients awaiting liver transplant due to NAFLD nearly tripled from 2004 to 2013, and in 2013 NAFLD became the second leading disease among waitlisted patients for liver transplantation.¹⁴ Dynamic Markov modeling predicts that cases of decompensated NASH cirrhosis (ie, liver failure) will rise by 161%, from about 144,000 to 376,000 cases over the next 15 years.⁸ These projections predict that NAFLD will overtake HCV as the leading cause of chronic liver disease among patients awaiting a liver transplant and will pose a significant clinical and economic burden in the coming years.

Aside from cirrhosis due to NAFLD, NAFLD-related HCC has been on the rise and has overtaken HCV-related HCC. UNOS data from 2003 to 2015 have shown a 2-fold decline in liver transplantation for HCV-associated HCC; however, the same period saw a 10-fold increase in liver transplantation for NAFLD-associated HCC.^15,16 This trend in NAFLD-related HCC is expected to grow from 5,000 to 6,000 cases in 2005 to 45,000 cases by 2025.⁹ More surprisingly, studies from the US veteran population have reported that patients with NAFLD-related HCC are less likely to have cirrhosis compared with patients with HCV- or alcohol-related HCC.¹⁷ Among all US veterans who developed HCC in the absence of cirrhosis between 2005 and 2010, NAFLD and metabolic syndrome seemed to be the leading risk factors for development of HCC.¹⁸ These trends raise concern for the rise in noncirrhotic HCC in the NAFLD population and highlight the need to improve current screening guidelines for this subset of patients.

Economic Burden

With such a heavy clinical burden and a projected increase in volume over the next decade, NAFLD is expected to have a similarly exponential impact on the economic burden. A review of 976 Medicare beneficiaries with NAFLD who were hospitalized from January 1, 2010 to December 31, 2010, noted a median annual total payment of about $11,000, with significantly lower payment for patients without cirrhosis compared with those with cirrhosis ($10,146 vs $18,804, P < .01).¹⁹ Another review of 29,528 Medicare beneficiaries with NAFLD who sought outpatient care between 2005 and 2010 saw a rise in mean yearly charges in 2005 of $2,624 ± 3,308 to $3,608 ± 5,132 in 2010 (P < .05).²⁰

To place these costs in perspective, Allen and colleagues reviewed a large national claims database of individuals enrolled with private and Medicare advantage health plans.²¹ Comparing patients with NAFLD with a control matched group with similar metabolic comorbidities the study revealed annual median outpatient care costs of $5,363 for the patients with NAFLD with Medicare advantage plans, which was significantly higher than $4,111 for the control group. Projection models based on similar Medicare beneficiaries estimate a rise in annual US economic burden to $103 billion from direct medical care costs alone and another $188 billion in societal costs related to NAFLD.²² New NASH/antifibrotic therapies are being evaluated in clinical trials and are expected to lead to even higher costs. Given the similarities in the trends of NAFLD prevalence between veterans and the general population, it is anticipated that a similar growth and burden in health care utilization cost will affect the VHA.

Association With Other Chronic Medical Conditions

NAFLD is closely associated with metabolic syndrome (Figure 3). Concurrent diagnosis of NAFLD in patients with existing T2DM is associated with poor glycemic control, progressive diabetic retinopathy, diabetic nephropathy, increased risk of cardiovascular complications, and a 2-fold increase in all-cause mortality.^1-3 

Similar associations have been described between NAFLD and other metabolic conditions such as obesity, hypertension, hypothyroidism, polycystic ovarian syndrome, and chronic kidney disease.³¹ Identifying patients with NAFLD may help with screening for the above metabolic diseases because patients with NAFLD (by comparison with patients with non-NAFLD) are at higher risk for diabetic, cardiovascular, and pulmonary complications and may warrant a more intensive treatment approach.

Conclusion

A leading cause of chronic liver disease and cirrhosis in the US, NAFLD is independently associated with metabolic syndrome and all-cause mortality. The number of veterans with NAFLD is expected to grow significantly over the coming years given the ongoing epidemic of adult and childhood obesity and T2DM. It is associated with many other medical conditions, including cardiovascular disease and complications, incident metabolic diseases, and may progress to liver cirrhosis and cirrhosis associated complications like HCC and liver failure. The current lack of any approved drug treatment for NASH/fibrosis and the shortage of organs for liver transplant emphasize the need for comprehensive primary prevention measures to reduce the future health and economic costs associated with NAFLD.

There is a growing need to address the epidemic of metabolic syndrome, as heralded by the World Health Organization in its 2013 global action plan. To address this multifaceted disease, initial approach should be to improve NAFLD education among veterans, beginning with the primary care teams and extending to specialty care, including hepatologists. Future steps also should include the development of a comprehensive metabolic/NAFLD clinic in all US Department of Veterans Affairs medical centers that integrates multidisciplinary care, point-of-care evaluation (eg, elastography staging of disease), and access to clinical trials, and have NAFLD care/outcome as a key performance target for all providers.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD also is an independent risk factor for cardiovascular disease, type 2 diabetes mellitus (T2DM), chronic kidney disease, cirrhosis, liver cancer, and all-cause mortality.^1-3 As the leading cause of liver disease in the US and globally, NAFLD is strongly associated with obesity and metabolic syndrome, with the rising prevalence of NAFLD closely mirroring the epidemic of obesity and T2DM.^4,5 The unrelenting increase of NAFLD prevalence has led to a significant rise in associated health care and economic burdens, compounded by the boom in childhood obesity and an aging population. In this review, we will discuss the epidemiology and economic burden of NAFLD in the US and how it affects veteran health.

NAFLD Definition

NAFLD is defined as the presence of > 5% of hepatic steatosis in the absence of excessive alcohol use, steatosis-inducing medication, or other concurrent chronic liver diseases. 

Compared with patients with NAFL, patients with NASH are at a much higher risk of developing fibrosis (scarring of the liver) and cirrhosis (significant scarring with distorted liver architecture). Patients with either NAFL or NASH, with or without advanced fibrosis, also can develop hepatocellular carcinoma (HCC). Severity of liver fibrosis (ie, fibrosis stage) is the most important predictor of liver-associated mortality and all-cause mortality; those with significant fibrosis (≥ F2 stage of fibrosis) are more likely to die of liver disease or to undergo a liver transplant compared with those with earlier stages of disease (ie, stages 0 to F1). Those with advanced scarring or cirrhosis (≥ F3 stage of fibrosis) exhibit an even higher risk of death or liver transplantation.⁶

NAFLD is a slow and often progressive disease. Time to progression between each stage of fibrosis is about 7 years; however, there has been a documented subset of patients with rapid progression to advanced fibrosis.⁷ The risk factors associated with this increased risk of fibrosis progression remain poorly understood.

Prevalence

The prevalence of NAFLD in the US is about 24% to 26%—about 85 million Americans. Up to 20% to 30% of these cases (about 17-25 million Americans) are thought to have NASH (Figure 2). 

Although liver biopsy remains the current gold standard for diagnosis and histopathologic staging of NAFLD, alternatives to liver biopsy include elastography techniques (ie, transient elastography using Fibroscan[Paris, France], shear wave elastography using Supersonic Image Aixplorer [Weston, FL], and magnetic resonance elastography), magnetic resonance spectroscopy, liver enzymes, and noninvasive simple and complex (serologic) scoring systems such as the Fatty Liver Index. Among these, liver enzymes and serologic scores are most likely to underestimate NAFLD disease burden. Transient elastographyis widely used because the test is easy to perform, noninvasive, and reliably estimates the degree of liver fibrosis in patients with NAFLD by measuring the speed of a mechanically induced shear wave using pulse-echo ultrasonic acquisitions in a much larger portion of the tissue (about 100 times more than a liver biopsy core). Transient elastography also can objectively quantify the amount of liver fat by measuring a 3.5 MHz ultrasound coefficient of attenuation or controlled attenuation parameter (CAP). This correlates with the degree of liver fat, and a higher CAP level reflects a greater degree of steatosis.

The largest study of US veterans utilized abnormal (ie, elevated) liver enzymes as the diagnostic criteria and reviewed nearly 10 million veterans who were followed between 2003 and 2011. Investigators reported a NAFLD prevalence of 13.6% in this population and noted an overall increase in NAFLD prevalence from 6.3% in 2003 to 17.6% in 2011, which highlights the continued growth in NAFLD clinical burden.¹⁰ This study, however, is likely to have underestimated the prevalence of NAFLD among veterans because liver enzymes are often normal among those with NAFLD (ie, low sensitivity), and the prevalence of obesity and T2DM are significantly higher in the veteran population vs the general population.

Incidence

There are limited studies on NAFLD incidence. The largest study of US veterans to date used liver enzymes as its diagnostic criteria and reported an annual NAFLD incidence of 2 to 3 per 100 persons (over 9 years from 2003 to 2011).¹⁰ There are a few studies from Asia and Europe, and a recent pooled meta-analysis of these studies reported the incidence of NAFLD in Asia to be 52.3 per 1,000 person-years; the incidence in Western countries was 28 per 1,000 person-years.⁵ These variances may be explained, in part, to disparities in race/background. For example, Hispanics and South Asians (ie, people from Bangladesh, India, or Pakistan) are at higher risk for NAFLD/NASH.¹¹ These findings reinforce the need for further studies to better estimate the true incidence of NAFLD among veterans.

Chronic Liver Disease, Cirrhosis, and Hepatocellular Carcinoma

The prevalence of NASH cirrhosis also has been evaluated using serologic scores, such as aspartate aminotransferase to platelet ratio index (APRI). The National Health and Nutrition Examination Survey (NHANES) database was reviewed, and data for adults in 2 separate periods were analyzed (1999-2002 and 2009-2012) and the prevalence of NASH cirrhosis was noted to have increased 2.5-fold over the period (0.072% vs 0.178%, P < .05).¹¹ Based on data from the HealthCore Integrated Research Database from 2006 to 2014, about 15% of cirrhosis cases were attributed to NAFLD, and about 24% each were attributed to hepatitis C virus (HCV) and alcoholic liver disease.¹² A review of about 60,000 veterans with cirrhosis between 2001 and 2013 revealed a prevalence of NAFLD-related cirrhosis of about 15%, while 48% were attributed to HCV.¹³ In contrast to the continued increase in NAFLD prevalence, the number of patients with HCV-associated liver disease has been in gradual decline since the advent of direct acting antiviral medications in 2011.¹²

Based on data from the United Network for Organ Sharing (UNOS), the number of patients awaiting liver transplant due to NAFLD nearly tripled from 2004 to 2013, and in 2013 NAFLD became the second leading disease among waitlisted patients for liver transplantation.¹⁴ Dynamic Markov modeling predicts that cases of decompensated NASH cirrhosis (ie, liver failure) will rise by 161%, from about 144,000 to 376,000 cases over the next 15 years.⁸ These projections predict that NAFLD will overtake HCV as the leading cause of chronic liver disease among patients awaiting a liver transplant and will pose a significant clinical and economic burden in the coming years.

Aside from cirrhosis due to NAFLD, NAFLD-related HCC has been on the rise and has overtaken HCV-related HCC. UNOS data from 2003 to 2015 have shown a 2-fold decline in liver transplantation for HCV-associated HCC; however, the same period saw a 10-fold increase in liver transplantation for NAFLD-associated HCC.^15,16 This trend in NAFLD-related HCC is expected to grow from 5,000 to 6,000 cases in 2005 to 45,000 cases by 2025.⁹ More surprisingly, studies from the US veteran population have reported that patients with NAFLD-related HCC are less likely to have cirrhosis compared with patients with HCV- or alcohol-related HCC.¹⁷ Among all US veterans who developed HCC in the absence of cirrhosis between 2005 and 2010, NAFLD and metabolic syndrome seemed to be the leading risk factors for development of HCC.¹⁸ These trends raise concern for the rise in noncirrhotic HCC in the NAFLD population and highlight the need to improve current screening guidelines for this subset of patients.

Economic Burden

With such a heavy clinical burden and a projected increase in volume over the next decade, NAFLD is expected to have a similarly exponential impact on the economic burden. A review of 976 Medicare beneficiaries with NAFLD who were hospitalized from January 1, 2010 to December 31, 2010, noted a median annual total payment of about $11,000, with significantly lower payment for patients without cirrhosis compared with those with cirrhosis ($10,146 vs $18,804, P < .01).¹⁹ Another review of 29,528 Medicare beneficiaries with NAFLD who sought outpatient care between 2005 and 2010 saw a rise in mean yearly charges in 2005 of $2,624 ± 3,308 to $3,608 ± 5,132 in 2010 (P < .05).²⁰

To place these costs in perspective, Allen and colleagues reviewed a large national claims database of individuals enrolled with private and Medicare advantage health plans.²¹ Comparing patients with NAFLD with a control matched group with similar metabolic comorbidities the study revealed annual median outpatient care costs of $5,363 for the patients with NAFLD with Medicare advantage plans, which was significantly higher than $4,111 for the control group. Projection models based on similar Medicare beneficiaries estimate a rise in annual US economic burden to $103 billion from direct medical care costs alone and another $188 billion in societal costs related to NAFLD.²² New NASH/antifibrotic therapies are being evaluated in clinical trials and are expected to lead to even higher costs. Given the similarities in the trends of NAFLD prevalence between veterans and the general population, it is anticipated that a similar growth and burden in health care utilization cost will affect the VHA.

Association With Other Chronic Medical Conditions

NAFLD is closely associated with metabolic syndrome (Figure 3). Concurrent diagnosis of NAFLD in patients with existing T2DM is associated with poor glycemic control, progressive diabetic retinopathy, diabetic nephropathy, increased risk of cardiovascular complications, and a 2-fold increase in all-cause mortality.^1-3 

Similar associations have been described between NAFLD and other metabolic conditions such as obesity, hypertension, hypothyroidism, polycystic ovarian syndrome, and chronic kidney disease.³¹ Identifying patients with NAFLD may help with screening for the above metabolic diseases because patients with NAFLD (by comparison with patients with non-NAFLD) are at higher risk for diabetic, cardiovascular, and pulmonary complications and may warrant a more intensive treatment approach.

Conclusion

A leading cause of chronic liver disease and cirrhosis in the US, NAFLD is independently associated with metabolic syndrome and all-cause mortality. The number of veterans with NAFLD is expected to grow significantly over the coming years given the ongoing epidemic of adult and childhood obesity and T2DM. It is associated with many other medical conditions, including cardiovascular disease and complications, incident metabolic diseases, and may progress to liver cirrhosis and cirrhosis associated complications like HCC and liver failure. The current lack of any approved drug treatment for NASH/fibrosis and the shortage of organs for liver transplant emphasize the need for comprehensive primary prevention measures to reduce the future health and economic costs associated with NAFLD.

There is a growing need to address the epidemic of metabolic syndrome, as heralded by the World Health Organization in its 2013 global action plan. To address this multifaceted disease, initial approach should be to improve NAFLD education among veterans, beginning with the primary care teams and extending to specialty care, including hepatologists. Future steps also should include the development of a comprehensive metabolic/NAFLD clinic in all US Department of Veterans Affairs medical centers that integrates multidisciplinary care, point-of-care evaluation (eg, elastography staging of disease), and access to clinical trials, and have NAFLD care/outcome as a key performance target for all providers.

For many years, viral hepatitis and particularly hepatitis C have been the bread and butter for clinicians dealing with chronic liver diseases. Over the past few years the Veterans Health Administration (VHA) has been incredibly successful in identifying, treating, and curing a significant proportion of veterans of this viral disease. However, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and will soon overtake hepatitis C virus as the leading cause of liver transplantation. NAFLD covers a disease spectrum ranging from nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis (NASH) to liver cirrhosis and liver cancer or liver failure. In the absence of effective treatment approaches, it is not surprising that NAFLD will create financial challenges for the VHA and US health care budgets. It is thus appropriate that Federal Practitioner has decided to publish a series of articles highlighting NAFLD and how it affects millions of Americans on its way to reaching quietly epidemic proportions within the VHA and across the globe.

Although NAFLD seems to have quietly and quickly reached epidemic proportions, its obscurity should not be surprising. NAFLD does not cause obvious symptoms in most patients, there is no simple test available for diagnosis of NASH, and disease-specific medications have not yet been approved for treatment. Primary care providers (PCPs) are the first point of medical contact for a majority of patients with or at risk for NAFLD; shockingly, NAFLD is greatly underrecognized, resulting in delayed diagnoses, which impact both health-related and quality-of-life outcomes in these patients. As emphasized in “Identifying and Treating Nonalcoholic Fatty Liver Disease” by Hunt and colleagues (page 20), PCPs should focus on 4 main aspects related to NAFLD: (1) Does my patient have NAFL? (2) Is my patient at risk for NASH and its ensuing manifestations? (3) Do simple noninvasive serum liver fibrosis markers suggest presence of clinically relevant liver fibrosis? and (4) Does my patient benefit from being referred to a specialist. The PCP is integral in optimally managing medical comorbidities and metabolic abnormalities as well as coordinating intense lifestyle and exercise interventions.

“Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans” by Shetty and Syn (page 14) discusses the epidemiology and economic burden of NAFLD in the US and how it will affect the health of veterans. Chronic liver disease is a major cause of mortality, morbidity, and health care resource utilization worldwide. Over the past 3 decades, NAFLD has gone from obscure liver diseases to the most common cause of chronic liver disease affecting 25% of the world’s population. Patients with NAFL who have advanced to NASH have an increased risk of liver-specific death. NASH is among the top etiologies for hepatocellular cancer and the fastest growing indication for liver transplantation, projected to overtake hepatitis C virus as the leading cause of liver transplantation. Most disturbing though is the fact that patients with NASH are the least likely to be surveyed for hepatocellular cancer development and the most likely to die while awaiting liver transplantation. Recent modeling estimates a 178% increase in liver deaths related to NASH by 2030.

The clinical burden of all stages of NAFLD is related to its prevalence, incidence, and progressiveness and has to be coupled with its tremendous economic burden based on inpatient, outpatient, professional services, emergency department, and pharmacy costs. It is thus not surprising that we are heading toward a serious health care crisis in the next few decades with the cost of managing NAFLD complications alone approaching an estimated 10-year economic burden of nearly $1 trillion.

The third article by Glass and colleagues (In press) puts the spectrum of NAFLD in the context of a disrupted systemic metabolic environment related to overnutrition alongside reduced physical activity. It is not surprising that type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease are frequent comorbidities present in a high proportion of patients with NAFLD. The prevalence of NAFLD among people with T2DM exceeds 60%. Importantly, convincing evidence has accumulated supporting the concept that interactions between these metabolic syndrome components and NAFLD are complex and bidirectional. Evidence from cross-sectional and longitudinal studies favors the presence of NAFLD and its severity preceding and/or promoting the development of metabolic comorbidities such as T2DM. Concomitantly, the presence of T2DM seems to accelerate the clinical course of NAFLD and is a predictor of advanced liver fibrosis and mortality. Compared with diseases that have a single etiology, such as viral hepatitis, NAFLD is a very complex disease with multiple interacting metabolic pathways that operate in an individual, leading to the clinical manifestation. Clearly, our present understanding of NAFLD/NASH as a single conglomerate disease is overly simplistic, and further study is warranted.

NAFLD and its variations comprise an increasing number and proportion of referral to hepatologists or providers with experience treating patients with chronic liver disease for the management of advanced disease stages; similarly, PCPs face the challenge to manage early stages of NAFLD. Given the magnitude of the problem of NAFLD, it is imperative that dedicated control efforts at the population level must intensify. As is emphasized in the fourth article of this series (In press), Puri and Fuchs call for a replacement of the traditional health care model of office visits with individual specialist working in silos. To overcome the narrow focus of a subspecialty outpatient clinic, time constraints, and gaps in NAFLD awareness, a patient-centered multidisciplinary approach to the treatment and coordination of care for the medically complex NAFLD patients is needed. The VHA is the largest integrated health care system in the US and is well positioned to implement an organizational strategy to facilitate standardized NAFLD care. The proposed model is centered on a broad assessment of the patient, involving the input from several disciplines; on completion of the assessment, a multidisciplinary team will formulate a personalized intervention plan.

The composition of this multidisciplinary team will vary based on expertise and resources available in each clinical setting. Once an intervention has been started, tracking and monitoring of intermediate and long-term functional outcomes will be helpful to modify the intervention in case outcomes are not achieved. Patient education, from the initial assessment until the intervention phase, plays a critical element to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals set with their health care team.

Ultimately, integration of health care services will lead to better quality of care, increased patient satisfaction, and importantly to improved health care service utilization that will reduce health care resources and costs. Although such a proposal may seem ambitious, it is now the time for innovative thinking that will create sustainable solutions for the silent epidemic of NAFLD. Without advancing a proactive vision, the VA and the world will soon become saddled with an unmanageable economic and health care burden.

For many years, viral hepatitis and particularly hepatitis C have been the bread and butter for clinicians dealing with chronic liver diseases. Over the past few years the Veterans Health Administration (VHA) has been incredibly successful in identifying, treating, and curing a significant proportion of veterans of this viral disease. However, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and will soon overtake hepatitis C virus as the leading cause of liver transplantation. NAFLD covers a disease spectrum ranging from nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis (NASH) to liver cirrhosis and liver cancer or liver failure. In the absence of effective treatment approaches, it is not surprising that NAFLD will create financial challenges for the VHA and US health care budgets. It is thus appropriate that Federal Practitioner has decided to publish a series of articles highlighting NAFLD and how it affects millions of Americans on its way to reaching quietly epidemic proportions within the VHA and across the globe.

Although NAFLD seems to have quietly and quickly reached epidemic proportions, its obscurity should not be surprising. NAFLD does not cause obvious symptoms in most patients, there is no simple test available for diagnosis of NASH, and disease-specific medications have not yet been approved for treatment. Primary care providers (PCPs) are the first point of medical contact for a majority of patients with or at risk for NAFLD; shockingly, NAFLD is greatly underrecognized, resulting in delayed diagnoses, which impact both health-related and quality-of-life outcomes in these patients. As emphasized in “Identifying and Treating Nonalcoholic Fatty Liver Disease” by Hunt and colleagues (page 20), PCPs should focus on 4 main aspects related to NAFLD: (1) Does my patient have NAFL? (2) Is my patient at risk for NASH and its ensuing manifestations? (3) Do simple noninvasive serum liver fibrosis markers suggest presence of clinically relevant liver fibrosis? and (4) Does my patient benefit from being referred to a specialist. The PCP is integral in optimally managing medical comorbidities and metabolic abnormalities as well as coordinating intense lifestyle and exercise interventions.

“Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans” by Shetty and Syn (page 14) discusses the epidemiology and economic burden of NAFLD in the US and how it will affect the health of veterans. Chronic liver disease is a major cause of mortality, morbidity, and health care resource utilization worldwide. Over the past 3 decades, NAFLD has gone from obscure liver diseases to the most common cause of chronic liver disease affecting 25% of the world’s population. Patients with NAFL who have advanced to NASH have an increased risk of liver-specific death. NASH is among the top etiologies for hepatocellular cancer and the fastest growing indication for liver transplantation, projected to overtake hepatitis C virus as the leading cause of liver transplantation. Most disturbing though is the fact that patients with NASH are the least likely to be surveyed for hepatocellular cancer development and the most likely to die while awaiting liver transplantation. Recent modeling estimates a 178% increase in liver deaths related to NASH by 2030.

The clinical burden of all stages of NAFLD is related to its prevalence, incidence, and progressiveness and has to be coupled with its tremendous economic burden based on inpatient, outpatient, professional services, emergency department, and pharmacy costs. It is thus not surprising that we are heading toward a serious health care crisis in the next few decades with the cost of managing NAFLD complications alone approaching an estimated 10-year economic burden of nearly $1 trillion.

The third article by Glass and colleagues (In press) puts the spectrum of NAFLD in the context of a disrupted systemic metabolic environment related to overnutrition alongside reduced physical activity. It is not surprising that type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease are frequent comorbidities present in a high proportion of patients with NAFLD. The prevalence of NAFLD among people with T2DM exceeds 60%. Importantly, convincing evidence has accumulated supporting the concept that interactions between these metabolic syndrome components and NAFLD are complex and bidirectional. Evidence from cross-sectional and longitudinal studies favors the presence of NAFLD and its severity preceding and/or promoting the development of metabolic comorbidities such as T2DM. Concomitantly, the presence of T2DM seems to accelerate the clinical course of NAFLD and is a predictor of advanced liver fibrosis and mortality. Compared with diseases that have a single etiology, such as viral hepatitis, NAFLD is a very complex disease with multiple interacting metabolic pathways that operate in an individual, leading to the clinical manifestation. Clearly, our present understanding of NAFLD/NASH as a single conglomerate disease is overly simplistic, and further study is warranted.

NAFLD and its variations comprise an increasing number and proportion of referral to hepatologists or providers with experience treating patients with chronic liver disease for the management of advanced disease stages; similarly, PCPs face the challenge to manage early stages of NAFLD. Given the magnitude of the problem of NAFLD, it is imperative that dedicated control efforts at the population level must intensify. As is emphasized in the fourth article of this series (In press), Puri and Fuchs call for a replacement of the traditional health care model of office visits with individual specialist working in silos. To overcome the narrow focus of a subspecialty outpatient clinic, time constraints, and gaps in NAFLD awareness, a patient-centered multidisciplinary approach to the treatment and coordination of care for the medically complex NAFLD patients is needed. The VHA is the largest integrated health care system in the US and is well positioned to implement an organizational strategy to facilitate standardized NAFLD care. The proposed model is centered on a broad assessment of the patient, involving the input from several disciplines; on completion of the assessment, a multidisciplinary team will formulate a personalized intervention plan.

The composition of this multidisciplinary team will vary based on expertise and resources available in each clinical setting. Once an intervention has been started, tracking and monitoring of intermediate and long-term functional outcomes will be helpful to modify the intervention in case outcomes are not achieved. Patient education, from the initial assessment until the intervention phase, plays a critical element to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals set with their health care team.

Ultimately, integration of health care services will lead to better quality of care, increased patient satisfaction, and importantly to improved health care service utilization that will reduce health care resources and costs. Although such a proposal may seem ambitious, it is now the time for innovative thinking that will create sustainable solutions for the silent epidemic of NAFLD. Without advancing a proactive vision, the VA and the world will soon become saddled with an unmanageable economic and health care burden.

For many years, viral hepatitis and particularly hepatitis C have been the bread and butter for clinicians dealing with chronic liver diseases. Over the past few years the Veterans Health Administration (VHA) has been incredibly successful in identifying, treating, and curing a significant proportion of veterans of this viral disease. However, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and will soon overtake hepatitis C virus as the leading cause of liver transplantation. NAFLD covers a disease spectrum ranging from nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis (NASH) to liver cirrhosis and liver cancer or liver failure. In the absence of effective treatment approaches, it is not surprising that NAFLD will create financial challenges for the VHA and US health care budgets. It is thus appropriate that Federal Practitioner has decided to publish a series of articles highlighting NAFLD and how it affects millions of Americans on its way to reaching quietly epidemic proportions within the VHA and across the globe.

Although NAFLD seems to have quietly and quickly reached epidemic proportions, its obscurity should not be surprising. NAFLD does not cause obvious symptoms in most patients, there is no simple test available for diagnosis of NASH, and disease-specific medications have not yet been approved for treatment. Primary care providers (PCPs) are the first point of medical contact for a majority of patients with or at risk for NAFLD; shockingly, NAFLD is greatly underrecognized, resulting in delayed diagnoses, which impact both health-related and quality-of-life outcomes in these patients. As emphasized in “Identifying and Treating Nonalcoholic Fatty Liver Disease” by Hunt and colleagues (page 20), PCPs should focus on 4 main aspects related to NAFLD: (1) Does my patient have NAFL? (2) Is my patient at risk for NASH and its ensuing manifestations? (3) Do simple noninvasive serum liver fibrosis markers suggest presence of clinically relevant liver fibrosis? and (4) Does my patient benefit from being referred to a specialist. The PCP is integral in optimally managing medical comorbidities and metabolic abnormalities as well as coordinating intense lifestyle and exercise interventions.

“Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans” by Shetty and Syn (page 14) discusses the epidemiology and economic burden of NAFLD in the US and how it will affect the health of veterans. Chronic liver disease is a major cause of mortality, morbidity, and health care resource utilization worldwide. Over the past 3 decades, NAFLD has gone from obscure liver diseases to the most common cause of chronic liver disease affecting 25% of the world’s population. Patients with NAFL who have advanced to NASH have an increased risk of liver-specific death. NASH is among the top etiologies for hepatocellular cancer and the fastest growing indication for liver transplantation, projected to overtake hepatitis C virus as the leading cause of liver transplantation. Most disturbing though is the fact that patients with NASH are the least likely to be surveyed for hepatocellular cancer development and the most likely to die while awaiting liver transplantation. Recent modeling estimates a 178% increase in liver deaths related to NASH by 2030.

The clinical burden of all stages of NAFLD is related to its prevalence, incidence, and progressiveness and has to be coupled with its tremendous economic burden based on inpatient, outpatient, professional services, emergency department, and pharmacy costs. It is thus not surprising that we are heading toward a serious health care crisis in the next few decades with the cost of managing NAFLD complications alone approaching an estimated 10-year economic burden of nearly $1 trillion.

The third article by Glass and colleagues (In press) puts the spectrum of NAFLD in the context of a disrupted systemic metabolic environment related to overnutrition alongside reduced physical activity. It is not surprising that type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease are frequent comorbidities present in a high proportion of patients with NAFLD. The prevalence of NAFLD among people with T2DM exceeds 60%. Importantly, convincing evidence has accumulated supporting the concept that interactions between these metabolic syndrome components and NAFLD are complex and bidirectional. Evidence from cross-sectional and longitudinal studies favors the presence of NAFLD and its severity preceding and/or promoting the development of metabolic comorbidities such as T2DM. Concomitantly, the presence of T2DM seems to accelerate the clinical course of NAFLD and is a predictor of advanced liver fibrosis and mortality. Compared with diseases that have a single etiology, such as viral hepatitis, NAFLD is a very complex disease with multiple interacting metabolic pathways that operate in an individual, leading to the clinical manifestation. Clearly, our present understanding of NAFLD/NASH as a single conglomerate disease is overly simplistic, and further study is warranted.

NAFLD and its variations comprise an increasing number and proportion of referral to hepatologists or providers with experience treating patients with chronic liver disease for the management of advanced disease stages; similarly, PCPs face the challenge to manage early stages of NAFLD. Given the magnitude of the problem of NAFLD, it is imperative that dedicated control efforts at the population level must intensify. As is emphasized in the fourth article of this series (In press), Puri and Fuchs call for a replacement of the traditional health care model of office visits with individual specialist working in silos. To overcome the narrow focus of a subspecialty outpatient clinic, time constraints, and gaps in NAFLD awareness, a patient-centered multidisciplinary approach to the treatment and coordination of care for the medically complex NAFLD patients is needed. The VHA is the largest integrated health care system in the US and is well positioned to implement an organizational strategy to facilitate standardized NAFLD care. The proposed model is centered on a broad assessment of the patient, involving the input from several disciplines; on completion of the assessment, a multidisciplinary team will formulate a personalized intervention plan.

The composition of this multidisciplinary team will vary based on expertise and resources available in each clinical setting. Once an intervention has been started, tracking and monitoring of intermediate and long-term functional outcomes will be helpful to modify the intervention in case outcomes are not achieved. Patient education, from the initial assessment until the intervention phase, plays a critical element to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals set with their health care team.

Ultimately, integration of health care services will lead to better quality of care, increased patient satisfaction, and importantly to improved health care service utilization that will reduce health care resources and costs. Although such a proposal may seem ambitious, it is now the time for innovative thinking that will create sustainable solutions for the silent epidemic of NAFLD. Without advancing a proactive vision, the VA and the world will soon become saddled with an unmanageable economic and health care burden.

Nonalcoholic fatty liver disease (NAFLD) is a silent epidemic affecting nearly 1 in 3 Americans and is increasing within the Veterans Health Administration (VHA).^1,2 NAFLD independently increases the risk of type 2 diabetes mellitus (T2DM), cardiovascular disease, chronic kidney disease, cirrhosis, liver cancer, and death and impairs health-related quality of life (QOL).³ NAFLD primarily affects those with metabolic risk factors (prediabetes, T2DM, and metabolic syndrome) or obesity (Figure 1).^4,5 

Among those with NAFLD, most have nonalcoholic fatty liver (NAFL), or simple steatosis, affecting > 5% of liver cells (Figure 2).¹² 

In most patients (80%), NAFLD progresses slowly over decades. The progression is related to continuing insulin resistance.^15,16 Greater disease progression is seen in patients with T2DM or concomitant chronic liver disease (such as hepatitis C).^10,11,16 Patients with NAFLD who develop advanced fibrosis or cirrhosis experience increased rates of overall mortality, liver-related events, and liver transplantation.^1,9,17,18 Within the VHA, NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 and 70 years, respectively.¹⁹Less commonly, HCC also can occur in NAFLD without cirrhosis.²⁰

Although no pharmaceuticals are yet approved to treat NAFLD, even modest weight loss is beneficial. For example, weight loss > 4% improves fatty liver, ≥ 7% improves liver inflammation, and ≥ 10% decreases liver fibrosis (or scarring).^21-23 In patients with a prior lack of success with weight loss, weight loss medications may be beneficial for short-term use.²⁴ When comparing the effects of diet, exercise, obesity pharmacotherapy, and combinations for these approaches, intensive lifestyle modification with exercise had the greatest, most enduring benefit.²⁵ Additionally, bariatric (weight loss) surgery has significantly improved health and liver-related outcomes for patients with NASH.²⁶

In at-risk veterans, NAFLD has myriad negative effects on health and QOL. To improve its early identification and management in the VHA, we summarize strategies that all providers can use to screen and treat patients for this condition.

Screening for Advanced Fibrosis

Advanced fibrosis in NAFLD is diagnosed by analyzing adequately sized liver biopsies.^27,28 However, noninvasive approaches to quantify advanced fibrosis by imaging or use of a simple fibrosis prediction score also are available. Imaging modalities include measuring liver stiffness, using transient elastography (FibroScan, Waltham, MA) or magnetic resonance elastography.^1,29-31 Fibrosis prediction scores use common clinical and laboratory data to predict the presence or absence of advanced fibrosis (Table 1).²⁹ 

Does This Patient Have NAFLD?

To identify NAFLD, patients with metabolic syndrome and modest or no alcohol use are first assessed for liver injury with ALT, AST, and complete blood count (Figure 3; Case 1).¹⁶ 

Next, common underlying liver diseases that cause liver injury should be excluded by hepatitis B and C virus serology.^11,16 Other underlying liver diseases are uncommon and should be assessed only if clinically indicated. 

Evaluation of fasting glucose or hemoglobin A_1c (HbA_1c)can identify undiagnosed T2DM. NAFL, or simple steatosis, is independently associated with an increased risk of T2DM, cardiovascular and kidney disease, yet not overall mortality.¹⁶ Over 10 to 20 years, few patients (4%) with simple steatosis progress to cirrhosis.³⁹In contrast, NAFLD advanced fibrosis significantly increases overall and liver-related mortality and can be assessed with high probability by calculating the patient’s FIB-4, even in those with normal liver enzymes.^11,16 Patients with highly probable advanced fibrosis merit evaluation by hepatology or gastroenterology (Figure 3).

In NAFLD, simple steatosis can resolve, and NASH can significantly improve with 7% to 10% weight loss.^16,23,40 Patients with simple steatosis on imaging and normal liver enzymes should be monitored with periodic liver enzymes and fibrosis prediction scores (eg, FIB-4) and encouraged to pursue intensive lifestyle intervention.^16,33 Without weight loss and exercise interventions metabolic syndrome, T2DM, and NAFLD may progress.

Patients with combined liver steatosis and liver enzyme elevations may exhibit NASH and warrant an evaluation by a hepatologist or gastroenterologist for consideration of additional testing or liver biopsy.¹⁶While ALT elevations often have been used as a marker of NASH, ALT can be normal in NASH and in advanced fibrosis.^41,42 A liver biopsy is required to establish the diagnosis of NASH, which progresses to cirrhosis in 15% to 20% over a 10- to 20-year follow-up period (Case 2).³⁹ Fibrosis prediction scores also can evaluate the probability of advanced fibrosis in these patients.

Encouraging Patients to Pursue Intensive Lifestyle InterventionS

Most veterans wish to collaborate in their care (Table 3, Figure 4) yet experience many barriers, such as low health literacy, high rates of comorbidities, and ongoing drug/alcohol misuse.^43,44 

In addition to patient education, motivational interviewing significantly improves weight loss, resulting in a 3.3 lb (1.5 kg) increased weight loss in the intervention group vs the control group in weight loss studies.⁴⁶By being supportive, empathic, and clearly sharing the rationale for change, motivational interviewing is a collaborative conversation to guide patients to strengthen their motivation and commitment to change.⁴⁷ It helps patients examine and address their ambivalence—most recognize they should exercise and lose weight, but it can be difficult.

To start the conversation, the health care provider can explain that NAFLD increases the risk of T2DM, heart disease, and liver injury or scarring and can be effectively treated (or improved) with modest weight loss and regular exercise (ie, 14 lb weight loss if 200 lb, or 21 lb weight loss if 300 lb). Exercise can start with a 5-minute walk and build to 30 minutes daily). Then, the provider can ask the following 4 questions:

1. Why would you want to lose weight and exercise?
2. How might you go about it in order to succeed?
3. What are the 3 best reasons for you to do it?
4. How important is it for you to make this change, and why? The provider can also ask the patient to quantify on a scale of 1 to 10: (a) How likely is it that they will make each required change? (b) How hard will each change be for them?
5. The provider then summarizes the patient’s reasons for wanting change, how he/she can effect change, what their best reasons are, and how to successfully change. The provider then asks a final question:
6. So what do you think you will do?

Most patients report feeling engaged, empowered, open, and understood with motivational interviewing. People are “persuaded by what they hear themselves say,” increasing motivation to change.⁴⁷

This personalized action plan facilitates successful health behavior change.⁴⁸ Action plans should integrate daily routines. For example, by placing the scale near the toothbrush, daily weighing is encouraged. Daily weighing is associated with significantly greater weight loss and less weight regain.⁴⁹ In a 6-month, randomized controlled weight loss trial in men and women, daily weighing (using a scale that automatically transmitted weight data), with weekly e-mails and tailored feedback yielded an overall 9% weight loss and increased use of exercise and diet behaviors associated with weight loss in comparison with those who weighed themselves less than weekly.⁵⁰ This simple daily measure seems to reinforce a patient’s action plan.

Adherence to an action plan significantly improves with patient education, peer or social support, and addressing barriers to adherence.⁵¹ For example, by providing support with weekly text messaging of “How are you?” and addressing the issues that patients reported in a large randomized treatment trial, adherence was significantly improved.⁵² In VHA patients with low health literacy, peer support or telephone coaching also has proven effective in increasing weight loss and glycemic control in patients with T2DM.^53,54 Providing multidisciplinary team support during intensive lifestyle intervention, providers can partner with patients to address questions or issues and applaud progress.

Effective VHA interventions

In an ethnically diverse population of patients with prediabetes, up to 7% weight loss was observed in the Diabetes Prevention Program (DPP).⁵⁵ In this study patients were randomized to placebo; metformin 850 mg twice daily; or a lifestyle-modification program in which they received one-on-one culturally sensitive, individualized lessons in diet, moderate exercise (≥ 150 minutes weekly), and behavior modification from case managers over 16 sessions. Lessons were reinforced in both group and individual sessions. This intervention was associated with an average of 6% weight loss at 6 months (half of participants attained 7% weight loss) and a 58% decrease in the rate of progression to T2DM over a nearly 3-year follow-up of this population with prediabetes compared with that of the placebo group.⁵⁵ Over a 15-year follow-up, the intensive lifestyle intervention group sustained a 27% decrease in the incidence of T2DM compared with that of the placebo group.⁵⁶ To emulate the success of the DPP in the VHA, a web-based DPP-like study in female veterans was performed with online coaching and daily weighing. This study achieved a 5.2% weight loss from baseline at 4 months.⁵⁷

To improve outcomes, the VHA MOVE! Weight Management Program has been revised to include more sustained intervention (16 sessions) and multiple modes for participating—in person, by telephone, via video, via MOVE! Coach phone app, or any combination.⁵⁸ Using shared decision making between patients with NAFLD and their providers, a customized MOVE! weight loss program can be developed to enable sustained intensive lifestyle intervention: hypocaloric diet, ≥ 150 minutes of moderate exercise weekly, and behavioral change.

In addition to intensive lifestyle intervention, a prospective study found that bariatric surgery significantly improved outcomes in patients with NASH, with most patients experiencing resolution of their NASH and nearly half exhibiting significantly improved fibrosis.²⁶ In the VHA, bariatric surgery has yielded excellent long-term outcomes, with 21% sustained weight loss from baseline (vs matched nonsurgical population) at 10 years postoperatively in patients undergoing Roux-en-Y gastric bypass.⁵⁹ Bariatric surgery also results in long-term remission of T2DM in most patients and significant improvement in hypertension and dyslipidemia.⁶⁰ The risks of bariatric surgery include 3% serious complications, 1% reoperation rates, and 0.4% 30-day mortality.^61,62 Bariatric surgery can be considered in patients with BMI > 40 or in patients with BMI > 35 who have comorbidities and do not have decompensated cirrhosis.^63,64

Beyond weight loss, more favorable liver-related outcomes and lower rates of advanced liver fibrosis are observed in those consuming filtered coffee; a reduction in liver steatosis also is observed with adherence to a Mediterranean diet.^65,66 In NAFLD, statins may improve liver chemistries and fibrosis; this class of medications can be used safely even in the presence of an elevated ALT.^11,67As a risk factor for chronic liver disease, alcohol consumption of ≥ 4 drinks per day or > 14 drinks per week for men or > 7 drinks per week for women should be avoided in patients with NAFLD.¹¹

Conclusion

Nonalcoholic fatty liver disease independently increases the risk of T2DM, cardiovascular disease and kidney disease. With its rates increasing in the VHA, earlier identification and intervention is warranted in patients at high risk (ie, those with metabolic syndrome, obesity, and T2DM).² 

NASH is more frequent in those with liver enzyme elevations or with an elevated FIB-4 and is associated with a long-term risk of cirrhosis. These patients merit referral to hepatology or gastroenterology for further evaluation and consideration of a liver biopsy to identify NASH. Patients with likely NAFLD without liver enzyme elevations can be further evaluated with FIB-4 scores to assess their probability of advanced liver fibrosis and potential need for referral to hepatology or gastroenterology.

Early NAFLD detection and intervention with intensive lifestyle modifications has the potential to avert progression to advanced fibrosis—and its associated increased overall and liver-related mortality, and impaired QOL.^3,16,18  Although FIB-4 is a validated predictor of advanced fibrosis, this score is not yet used nationally to identify and risk stratify NAFLD in the VHA. Additionally, the very low use of VHA diet/exercise programs in eligible patients contributes to NAFLD progression.⁶⁸ The cost-effective DPP has successfully yielded weight loss in patients with prediabetes and decreases in the incidence of T2DM through motivational interviewing and intensive lifestyle intervention.⁵⁵ 

To improve NAFLD management, providers can successfully engage patients through motivational interviewing for intensive lifestyle intervention. Their resulting weight loss is enhanced with a personalized action plan, daily weighing, and peer support. When NAFLD is identified in patients with metabolic risk factors, the probability of advanced fibrosis is easily assessed in those with elevated FIB-4 scores who merit gastrointestinal referral.^33,37

In all those identified with NAFLD, disease information should be provided to patients and their families. Intensive lifestyle modification targeting a ≥ 7% weight loss is recommended; motivational interviewing can increase commitment to change and yield a customized action plan for sustained weight loss. Working with the support and encouragement of their team of primary care providers, dieticians, and MOVE! coaches, patients can actively engage to improve their NAFLD and overall health.

Nonalcoholic fatty liver disease (NAFLD) is a silent epidemic affecting nearly 1 in 3 Americans and is increasing within the Veterans Health Administration (VHA).^1,2 NAFLD independently increases the risk of type 2 diabetes mellitus (T2DM), cardiovascular disease, chronic kidney disease, cirrhosis, liver cancer, and death and impairs health-related quality of life (QOL).³ NAFLD primarily affects those with metabolic risk factors (prediabetes, T2DM, and metabolic syndrome) or obesity (Figure 1).^4,5 

Among those with NAFLD, most have nonalcoholic fatty liver (NAFL), or simple steatosis, affecting > 5% of liver cells (Figure 2).¹² 

In most patients (80%), NAFLD progresses slowly over decades. The progression is related to continuing insulin resistance.^15,16 Greater disease progression is seen in patients with T2DM or concomitant chronic liver disease (such as hepatitis C).^10,11,16 Patients with NAFLD who develop advanced fibrosis or cirrhosis experience increased rates of overall mortality, liver-related events, and liver transplantation.^1,9,17,18 Within the VHA, NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 and 70 years, respectively.¹⁹Less commonly, HCC also can occur in NAFLD without cirrhosis.²⁰

Although no pharmaceuticals are yet approved to treat NAFLD, even modest weight loss is beneficial. For example, weight loss > 4% improves fatty liver, ≥ 7% improves liver inflammation, and ≥ 10% decreases liver fibrosis (or scarring).^21-23 In patients with a prior lack of success with weight loss, weight loss medications may be beneficial for short-term use.²⁴ When comparing the effects of diet, exercise, obesity pharmacotherapy, and combinations for these approaches, intensive lifestyle modification with exercise had the greatest, most enduring benefit.²⁵ Additionally, bariatric (weight loss) surgery has significantly improved health and liver-related outcomes for patients with NASH.²⁶

In at-risk veterans, NAFLD has myriad negative effects on health and QOL. To improve its early identification and management in the VHA, we summarize strategies that all providers can use to screen and treat patients for this condition.

Screening for Advanced Fibrosis

Advanced fibrosis in NAFLD is diagnosed by analyzing adequately sized liver biopsies.^27,28 However, noninvasive approaches to quantify advanced fibrosis by imaging or use of a simple fibrosis prediction score also are available. Imaging modalities include measuring liver stiffness, using transient elastography (FibroScan, Waltham, MA) or magnetic resonance elastography.^1,29-31 Fibrosis prediction scores use common clinical and laboratory data to predict the presence or absence of advanced fibrosis (Table 1).²⁹ 

Does This Patient Have NAFLD?

To identify NAFLD, patients with metabolic syndrome and modest or no alcohol use are first assessed for liver injury with ALT, AST, and complete blood count (Figure 3; Case 1).¹⁶ 

Next, common underlying liver diseases that cause liver injury should be excluded by hepatitis B and C virus serology.^11,16 Other underlying liver diseases are uncommon and should be assessed only if clinically indicated. 

Evaluation of fasting glucose or hemoglobin A_1c (HbA_1c)can identify undiagnosed T2DM. NAFL, or simple steatosis, is independently associated with an increased risk of T2DM, cardiovascular and kidney disease, yet not overall mortality.¹⁶ Over 10 to 20 years, few patients (4%) with simple steatosis progress to cirrhosis.³⁹In contrast, NAFLD advanced fibrosis significantly increases overall and liver-related mortality and can be assessed with high probability by calculating the patient’s FIB-4, even in those with normal liver enzymes.^11,16 Patients with highly probable advanced fibrosis merit evaluation by hepatology or gastroenterology (Figure 3).

In NAFLD, simple steatosis can resolve, and NASH can significantly improve with 7% to 10% weight loss.^16,23,40 Patients with simple steatosis on imaging and normal liver enzymes should be monitored with periodic liver enzymes and fibrosis prediction scores (eg, FIB-4) and encouraged to pursue intensive lifestyle intervention.^16,33 Without weight loss and exercise interventions metabolic syndrome, T2DM, and NAFLD may progress.

Patients with combined liver steatosis and liver enzyme elevations may exhibit NASH and warrant an evaluation by a hepatologist or gastroenterologist for consideration of additional testing or liver biopsy.¹⁶While ALT elevations often have been used as a marker of NASH, ALT can be normal in NASH and in advanced fibrosis.^41,42 A liver biopsy is required to establish the diagnosis of NASH, which progresses to cirrhosis in 15% to 20% over a 10- to 20-year follow-up period (Case 2).³⁹ Fibrosis prediction scores also can evaluate the probability of advanced fibrosis in these patients.

Encouraging Patients to Pursue Intensive Lifestyle InterventionS

Most veterans wish to collaborate in their care (Table 3, Figure 4) yet experience many barriers, such as low health literacy, high rates of comorbidities, and ongoing drug/alcohol misuse.^43,44 

In addition to patient education, motivational interviewing significantly improves weight loss, resulting in a 3.3 lb (1.5 kg) increased weight loss in the intervention group vs the control group in weight loss studies.⁴⁶By being supportive, empathic, and clearly sharing the rationale for change, motivational interviewing is a collaborative conversation to guide patients to strengthen their motivation and commitment to change.⁴⁷ It helps patients examine and address their ambivalence—most recognize they should exercise and lose weight, but it can be difficult.

To start the conversation, the health care provider can explain that NAFLD increases the risk of T2DM, heart disease, and liver injury or scarring and can be effectively treated (or improved) with modest weight loss and regular exercise (ie, 14 lb weight loss if 200 lb, or 21 lb weight loss if 300 lb). Exercise can start with a 5-minute walk and build to 30 minutes daily). Then, the provider can ask the following 4 questions:

1. Why would you want to lose weight and exercise?
2. How might you go about it in order to succeed?
3. What are the 3 best reasons for you to do it?
4. How important is it for you to make this change, and why? The provider can also ask the patient to quantify on a scale of 1 to 10: (a) How likely is it that they will make each required change? (b) How hard will each change be for them?
5. The provider then summarizes the patient’s reasons for wanting change, how he/she can effect change, what their best reasons are, and how to successfully change. The provider then asks a final question:
6. So what do you think you will do?

Most patients report feeling engaged, empowered, open, and understood with motivational interviewing. People are “persuaded by what they hear themselves say,” increasing motivation to change.⁴⁷

This personalized action plan facilitates successful health behavior change.⁴⁸ Action plans should integrate daily routines. For example, by placing the scale near the toothbrush, daily weighing is encouraged. Daily weighing is associated with significantly greater weight loss and less weight regain.⁴⁹ In a 6-month, randomized controlled weight loss trial in men and women, daily weighing (using a scale that automatically transmitted weight data), with weekly e-mails and tailored feedback yielded an overall 9% weight loss and increased use of exercise and diet behaviors associated with weight loss in comparison with those who weighed themselves less than weekly.⁵⁰ This simple daily measure seems to reinforce a patient’s action plan.

Adherence to an action plan significantly improves with patient education, peer or social support, and addressing barriers to adherence.⁵¹ For example, by providing support with weekly text messaging of “How are you?” and addressing the issues that patients reported in a large randomized treatment trial, adherence was significantly improved.⁵² In VHA patients with low health literacy, peer support or telephone coaching also has proven effective in increasing weight loss and glycemic control in patients with T2DM.^53,54 Providing multidisciplinary team support during intensive lifestyle intervention, providers can partner with patients to address questions or issues and applaud progress.

Effective VHA interventions

In an ethnically diverse population of patients with prediabetes, up to 7% weight loss was observed in the Diabetes Prevention Program (DPP).⁵⁵ In this study patients were randomized to placebo; metformin 850 mg twice daily; or a lifestyle-modification program in which they received one-on-one culturally sensitive, individualized lessons in diet, moderate exercise (≥ 150 minutes weekly), and behavior modification from case managers over 16 sessions. Lessons were reinforced in both group and individual sessions. This intervention was associated with an average of 6% weight loss at 6 months (half of participants attained 7% weight loss) and a 58% decrease in the rate of progression to T2DM over a nearly 3-year follow-up of this population with prediabetes compared with that of the placebo group.⁵⁵ Over a 15-year follow-up, the intensive lifestyle intervention group sustained a 27% decrease in the incidence of T2DM compared with that of the placebo group.⁵⁶ To emulate the success of the DPP in the VHA, a web-based DPP-like study in female veterans was performed with online coaching and daily weighing. This study achieved a 5.2% weight loss from baseline at 4 months.⁵⁷

To improve outcomes, the VHA MOVE! Weight Management Program has been revised to include more sustained intervention (16 sessions) and multiple modes for participating—in person, by telephone, via video, via MOVE! Coach phone app, or any combination.⁵⁸ Using shared decision making between patients with NAFLD and their providers, a customized MOVE! weight loss program can be developed to enable sustained intensive lifestyle intervention: hypocaloric diet, ≥ 150 minutes of moderate exercise weekly, and behavioral change.

In addition to intensive lifestyle intervention, a prospective study found that bariatric surgery significantly improved outcomes in patients with NASH, with most patients experiencing resolution of their NASH and nearly half exhibiting significantly improved fibrosis.²⁶ In the VHA, bariatric surgery has yielded excellent long-term outcomes, with 21% sustained weight loss from baseline (vs matched nonsurgical population) at 10 years postoperatively in patients undergoing Roux-en-Y gastric bypass.⁵⁹ Bariatric surgery also results in long-term remission of T2DM in most patients and significant improvement in hypertension and dyslipidemia.⁶⁰ The risks of bariatric surgery include 3% serious complications, 1% reoperation rates, and 0.4% 30-day mortality.^61,62 Bariatric surgery can be considered in patients with BMI > 40 or in patients with BMI > 35 who have comorbidities and do not have decompensated cirrhosis.^63,64

Beyond weight loss, more favorable liver-related outcomes and lower rates of advanced liver fibrosis are observed in those consuming filtered coffee; a reduction in liver steatosis also is observed with adherence to a Mediterranean diet.^65,66 In NAFLD, statins may improve liver chemistries and fibrosis; this class of medications can be used safely even in the presence of an elevated ALT.^11,67As a risk factor for chronic liver disease, alcohol consumption of ≥ 4 drinks per day or > 14 drinks per week for men or > 7 drinks per week for women should be avoided in patients with NAFLD.¹¹

Conclusion

Nonalcoholic fatty liver disease independently increases the risk of T2DM, cardiovascular disease and kidney disease. With its rates increasing in the VHA, earlier identification and intervention is warranted in patients at high risk (ie, those with metabolic syndrome, obesity, and T2DM).² 

NASH is more frequent in those with liver enzyme elevations or with an elevated FIB-4 and is associated with a long-term risk of cirrhosis. These patients merit referral to hepatology or gastroenterology for further evaluation and consideration of a liver biopsy to identify NASH. Patients with likely NAFLD without liver enzyme elevations can be further evaluated with FIB-4 scores to assess their probability of advanced liver fibrosis and potential need for referral to hepatology or gastroenterology.

Early NAFLD detection and intervention with intensive lifestyle modifications has the potential to avert progression to advanced fibrosis—and its associated increased overall and liver-related mortality, and impaired QOL.^3,16,18  Although FIB-4 is a validated predictor of advanced fibrosis, this score is not yet used nationally to identify and risk stratify NAFLD in the VHA. Additionally, the very low use of VHA diet/exercise programs in eligible patients contributes to NAFLD progression.⁶⁸ The cost-effective DPP has successfully yielded weight loss in patients with prediabetes and decreases in the incidence of T2DM through motivational interviewing and intensive lifestyle intervention.⁵⁵ 

To improve NAFLD management, providers can successfully engage patients through motivational interviewing for intensive lifestyle intervention. Their resulting weight loss is enhanced with a personalized action plan, daily weighing, and peer support. When NAFLD is identified in patients with metabolic risk factors, the probability of advanced fibrosis is easily assessed in those with elevated FIB-4 scores who merit gastrointestinal referral.^33,37

In all those identified with NAFLD, disease information should be provided to patients and their families. Intensive lifestyle modification targeting a ≥ 7% weight loss is recommended; motivational interviewing can increase commitment to change and yield a customized action plan for sustained weight loss. Working with the support and encouragement of their team of primary care providers, dieticians, and MOVE! coaches, patients can actively engage to improve their NAFLD and overall health.

Nonalcoholic fatty liver disease (NAFLD) is a silent epidemic affecting nearly 1 in 3 Americans and is increasing within the Veterans Health Administration (VHA).^1,2 NAFLD independently increases the risk of type 2 diabetes mellitus (T2DM), cardiovascular disease, chronic kidney disease, cirrhosis, liver cancer, and death and impairs health-related quality of life (QOL).³ NAFLD primarily affects those with metabolic risk factors (prediabetes, T2DM, and metabolic syndrome) or obesity (Figure 1).^4,5 

Among those with NAFLD, most have nonalcoholic fatty liver (NAFL), or simple steatosis, affecting > 5% of liver cells (Figure 2).¹² 

In most patients (80%), NAFLD progresses slowly over decades. The progression is related to continuing insulin resistance.^15,16 Greater disease progression is seen in patients with T2DM or concomitant chronic liver disease (such as hepatitis C).^10,11,16 Patients with NAFLD who develop advanced fibrosis or cirrhosis experience increased rates of overall mortality, liver-related events, and liver transplantation.^1,9,17,18 Within the VHA, NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 and 70 years, respectively.¹⁹Less commonly, HCC also can occur in NAFLD without cirrhosis.²⁰

Although no pharmaceuticals are yet approved to treat NAFLD, even modest weight loss is beneficial. For example, weight loss > 4% improves fatty liver, ≥ 7% improves liver inflammation, and ≥ 10% decreases liver fibrosis (or scarring).^21-23 In patients with a prior lack of success with weight loss, weight loss medications may be beneficial for short-term use.²⁴ When comparing the effects of diet, exercise, obesity pharmacotherapy, and combinations for these approaches, intensive lifestyle modification with exercise had the greatest, most enduring benefit.²⁵ Additionally, bariatric (weight loss) surgery has significantly improved health and liver-related outcomes for patients with NASH.²⁶

In at-risk veterans, NAFLD has myriad negative effects on health and QOL. To improve its early identification and management in the VHA, we summarize strategies that all providers can use to screen and treat patients for this condition.

Screening for Advanced Fibrosis

Advanced fibrosis in NAFLD is diagnosed by analyzing adequately sized liver biopsies.^27,28 However, noninvasive approaches to quantify advanced fibrosis by imaging or use of a simple fibrosis prediction score also are available. Imaging modalities include measuring liver stiffness, using transient elastography (FibroScan, Waltham, MA) or magnetic resonance elastography.^1,29-31 Fibrosis prediction scores use common clinical and laboratory data to predict the presence or absence of advanced fibrosis (Table 1).²⁹ 

Does This Patient Have NAFLD?

To identify NAFLD, patients with metabolic syndrome and modest or no alcohol use are first assessed for liver injury with ALT, AST, and complete blood count (Figure 3; Case 1).¹⁶ 

Next, common underlying liver diseases that cause liver injury should be excluded by hepatitis B and C virus serology.^11,16 Other underlying liver diseases are uncommon and should be assessed only if clinically indicated. 

Evaluation of fasting glucose or hemoglobin A_1c (HbA_1c)can identify undiagnosed T2DM. NAFL, or simple steatosis, is independently associated with an increased risk of T2DM, cardiovascular and kidney disease, yet not overall mortality.¹⁶ Over 10 to 20 years, few patients (4%) with simple steatosis progress to cirrhosis.³⁹In contrast, NAFLD advanced fibrosis significantly increases overall and liver-related mortality and can be assessed with high probability by calculating the patient’s FIB-4, even in those with normal liver enzymes.^11,16 Patients with highly probable advanced fibrosis merit evaluation by hepatology or gastroenterology (Figure 3).

In NAFLD, simple steatosis can resolve, and NASH can significantly improve with 7% to 10% weight loss.^16,23,40 Patients with simple steatosis on imaging and normal liver enzymes should be monitored with periodic liver enzymes and fibrosis prediction scores (eg, FIB-4) and encouraged to pursue intensive lifestyle intervention.^16,33 Without weight loss and exercise interventions metabolic syndrome, T2DM, and NAFLD may progress.

Patients with combined liver steatosis and liver enzyme elevations may exhibit NASH and warrant an evaluation by a hepatologist or gastroenterologist for consideration of additional testing or liver biopsy.¹⁶While ALT elevations often have been used as a marker of NASH, ALT can be normal in NASH and in advanced fibrosis.^41,42 A liver biopsy is required to establish the diagnosis of NASH, which progresses to cirrhosis in 15% to 20% over a 10- to 20-year follow-up period (Case 2).³⁹ Fibrosis prediction scores also can evaluate the probability of advanced fibrosis in these patients.

Encouraging Patients to Pursue Intensive Lifestyle InterventionS

Most veterans wish to collaborate in their care (Table 3, Figure 4) yet experience many barriers, such as low health literacy, high rates of comorbidities, and ongoing drug/alcohol misuse.^43,44 

In addition to patient education, motivational interviewing significantly improves weight loss, resulting in a 3.3 lb (1.5 kg) increased weight loss in the intervention group vs the control group in weight loss studies.⁴⁶By being supportive, empathic, and clearly sharing the rationale for change, motivational interviewing is a collaborative conversation to guide patients to strengthen their motivation and commitment to change.⁴⁷ It helps patients examine and address their ambivalence—most recognize they should exercise and lose weight, but it can be difficult.

To start the conversation, the health care provider can explain that NAFLD increases the risk of T2DM, heart disease, and liver injury or scarring and can be effectively treated (or improved) with modest weight loss and regular exercise (ie, 14 lb weight loss if 200 lb, or 21 lb weight loss if 300 lb). Exercise can start with a 5-minute walk and build to 30 minutes daily). Then, the provider can ask the following 4 questions:

1. Why would you want to lose weight and exercise?
2. How might you go about it in order to succeed?
3. What are the 3 best reasons for you to do it?
4. How important is it for you to make this change, and why? The provider can also ask the patient to quantify on a scale of 1 to 10: (a) How likely is it that they will make each required change? (b) How hard will each change be for them?
5. The provider then summarizes the patient’s reasons for wanting change, how he/she can effect change, what their best reasons are, and how to successfully change. The provider then asks a final question:
6. So what do you think you will do?

Most patients report feeling engaged, empowered, open, and understood with motivational interviewing. People are “persuaded by what they hear themselves say,” increasing motivation to change.⁴⁷

This personalized action plan facilitates successful health behavior change.⁴⁸ Action plans should integrate daily routines. For example, by placing the scale near the toothbrush, daily weighing is encouraged. Daily weighing is associated with significantly greater weight loss and less weight regain.⁴⁹ In a 6-month, randomized controlled weight loss trial in men and women, daily weighing (using a scale that automatically transmitted weight data), with weekly e-mails and tailored feedback yielded an overall 9% weight loss and increased use of exercise and diet behaviors associated with weight loss in comparison with those who weighed themselves less than weekly.⁵⁰ This simple daily measure seems to reinforce a patient’s action plan.

Adherence to an action plan significantly improves with patient education, peer or social support, and addressing barriers to adherence.⁵¹ For example, by providing support with weekly text messaging of “How are you?” and addressing the issues that patients reported in a large randomized treatment trial, adherence was significantly improved.⁵² In VHA patients with low health literacy, peer support or telephone coaching also has proven effective in increasing weight loss and glycemic control in patients with T2DM.^53,54 Providing multidisciplinary team support during intensive lifestyle intervention, providers can partner with patients to address questions or issues and applaud progress.

Effective VHA interventions

In an ethnically diverse population of patients with prediabetes, up to 7% weight loss was observed in the Diabetes Prevention Program (DPP).⁵⁵ In this study patients were randomized to placebo; metformin 850 mg twice daily; or a lifestyle-modification program in which they received one-on-one culturally sensitive, individualized lessons in diet, moderate exercise (≥ 150 minutes weekly), and behavior modification from case managers over 16 sessions. Lessons were reinforced in both group and individual sessions. This intervention was associated with an average of 6% weight loss at 6 months (half of participants attained 7% weight loss) and a 58% decrease in the rate of progression to T2DM over a nearly 3-year follow-up of this population with prediabetes compared with that of the placebo group.⁵⁵ Over a 15-year follow-up, the intensive lifestyle intervention group sustained a 27% decrease in the incidence of T2DM compared with that of the placebo group.⁵⁶ To emulate the success of the DPP in the VHA, a web-based DPP-like study in female veterans was performed with online coaching and daily weighing. This study achieved a 5.2% weight loss from baseline at 4 months.⁵⁷

To improve outcomes, the VHA MOVE! Weight Management Program has been revised to include more sustained intervention (16 sessions) and multiple modes for participating—in person, by telephone, via video, via MOVE! Coach phone app, or any combination.⁵⁸ Using shared decision making between patients with NAFLD and their providers, a customized MOVE! weight loss program can be developed to enable sustained intensive lifestyle intervention: hypocaloric diet, ≥ 150 minutes of moderate exercise weekly, and behavioral change.

In addition to intensive lifestyle intervention, a prospective study found that bariatric surgery significantly improved outcomes in patients with NASH, with most patients experiencing resolution of their NASH and nearly half exhibiting significantly improved fibrosis.²⁶ In the VHA, bariatric surgery has yielded excellent long-term outcomes, with 21% sustained weight loss from baseline (vs matched nonsurgical population) at 10 years postoperatively in patients undergoing Roux-en-Y gastric bypass.⁵⁹ Bariatric surgery also results in long-term remission of T2DM in most patients and significant improvement in hypertension and dyslipidemia.⁶⁰ The risks of bariatric surgery include 3% serious complications, 1% reoperation rates, and 0.4% 30-day mortality.^61,62 Bariatric surgery can be considered in patients with BMI > 40 or in patients with BMI > 35 who have comorbidities and do not have decompensated cirrhosis.^63,64

Beyond weight loss, more favorable liver-related outcomes and lower rates of advanced liver fibrosis are observed in those consuming filtered coffee; a reduction in liver steatosis also is observed with adherence to a Mediterranean diet.^65,66 In NAFLD, statins may improve liver chemistries and fibrosis; this class of medications can be used safely even in the presence of an elevated ALT.^11,67As a risk factor for chronic liver disease, alcohol consumption of ≥ 4 drinks per day or > 14 drinks per week for men or > 7 drinks per week for women should be avoided in patients with NAFLD.¹¹

Conclusion

Nonalcoholic fatty liver disease independently increases the risk of T2DM, cardiovascular disease and kidney disease. With its rates increasing in the VHA, earlier identification and intervention is warranted in patients at high risk (ie, those with metabolic syndrome, obesity, and T2DM).² 

NASH is more frequent in those with liver enzyme elevations or with an elevated FIB-4 and is associated with a long-term risk of cirrhosis. These patients merit referral to hepatology or gastroenterology for further evaluation and consideration of a liver biopsy to identify NASH. Patients with likely NAFLD without liver enzyme elevations can be further evaluated with FIB-4 scores to assess their probability of advanced liver fibrosis and potential need for referral to hepatology or gastroenterology.

Early NAFLD detection and intervention with intensive lifestyle modifications has the potential to avert progression to advanced fibrosis—and its associated increased overall and liver-related mortality, and impaired QOL.^3,16,18  Although FIB-4 is a validated predictor of advanced fibrosis, this score is not yet used nationally to identify and risk stratify NAFLD in the VHA. Additionally, the very low use of VHA diet/exercise programs in eligible patients contributes to NAFLD progression.⁶⁸ The cost-effective DPP has successfully yielded weight loss in patients with prediabetes and decreases in the incidence of T2DM through motivational interviewing and intensive lifestyle intervention.⁵⁵ 

To improve NAFLD management, providers can successfully engage patients through motivational interviewing for intensive lifestyle intervention. Their resulting weight loss is enhanced with a personalized action plan, daily weighing, and peer support. When NAFLD is identified in patients with metabolic risk factors, the probability of advanced fibrosis is easily assessed in those with elevated FIB-4 scores who merit gastrointestinal referral.^33,37

In all those identified with NAFLD, disease information should be provided to patients and their families. Intensive lifestyle modification targeting a ≥ 7% weight loss is recommended; motivational interviewing can increase commitment to change and yield a customized action plan for sustained weight loss. Working with the support and encouragement of their team of primary care providers, dieticians, and MOVE! coaches, patients can actively engage to improve their NAFLD and overall health.

Idiopathic granulomatous mastitis (IGM) is rare during pregnancy; it typically is seen in women of childbearing potential from 6 months to 6 years postpartum.¹ Because of a temporal association with breastfeeding, it is believed that hyperprolactinemia² or an immune response to local lobular secretions might play a role in pathogenesis. Early misdiagnosis as bacterial mastitis is common, prompting multiple antibiotic regimens. When antibiotics fail, patients are worked up for inflammatory breast cancer, given the nonhealing breast nodules. Mammography, ultrasonography, and fine-needle aspiration often are unable to rule out carcinoma, warranting excisional biopsies of nodules. The patient is then referred to rheumatology for potential sarcoidosis or to dermatology for IGM. In either case, the workup should be similar, but additional history focused on behavior and medications is essential in suspected IGM, given the association with hyperprolactinemia.

Because IGM is rare, there are no randomized, placebo-controlled trials of treatment efficacy. In many cases, patients undergo complete mastectomy, which is curative but may be psychologically and physically impactful in young women. In some cases, high-dose corticosteroids have been successful; however, because the IGM process can last longer than 2 years, patients treated in this manner are exposed to steroid morbidities.¹

We report 3 cases of IGM that add to the literature on possible contributing factors, clinical presentations, and treatments for this disease. We also demonstrate that appropriate trigger identification and steroid-sparing agents, specifically methotrexate, can be breast-saving as they can alleviate this debilitating condition, obviating the need for radical surgical intervention.

CASE REPORTS 

Patient 1

A 40-year-old woman with a 4-year history of breastfeeding noted a grape-sized nodule on the left breast that grew to the size of a grapefruit after 2 weeks. Ulceration and drainage periodically occurred, forming pink plaques along the lateral aspects of the breast after healing. Her primary care provider suspected infectious mastitis; she was given an oral antibiotic (cephalexin) and intravenous antibiotics without improvement.

Imaging
Subsequent magnetic resonance imaging revealed a large, irregular, enhancing mass within the outer left breast (6.5 cm at greatest dimension) with additional surrounding amorphous enhancement highly suspicious for malignancy. There also were multiple prominent left axillary lymph nodes, with the largest demonstrating a cortical thickness of 8 mm.

Biopsy
Core breast biopsy showed benign tissue with fat necrosis. Fine-needle aspiration revealed few benign ductal cells and rare histiocytes; because these findings were nondiagnostic and cancer was still a consideration, the patient underwent excisional biopsy.

Histologic sections of breast tissue showed extensive lobulocentric inflammation comprising histiocytes and lymphocytes, with neutrophils admixed and forming microabscesses (Figure 1A). Multinucleated giant cells and single-cell necrosis were seen, but true caseous necrosis was absent (Figure 1B). Duct spaces often contained inflammatory cells or secretions. Special stains for fungal and acid-fast bacterial microorganisms were negative.

Granulomatous lobular mastitis was diagnosed, and the patient was referred to dermatology. On presentation to dermatology, the left breast showed a 6-cm area of firm induration and overlying peau d’orange change to the epidermis (Figure 2A). Based on pathologic analysis, she was worked up for a possible granulomatous etiology. Negative purified protein derivative (tuberculin)(PPD) and a normal chest radiograph ruled out tuberculosis. Normal chest radiography, serum Ca²⁺ and angiotensin-converting enzyme (ACE) levels, and ophthalmology examination ruled out sarcoidosis.

The patient reported she continued breastfeeding her 4-year-old son. Additionally, she had been started on trazadone and buspirone for alcohol abuse recovery, then switched to and maintained on fluoxetine 1 year before developing these symptoms.

Buspirone, fluoxetine, and prolonged breastfeeding all contribute to hyperprolactinemia, a possible trigger of IGM. The patient was therefore advised to stop breastfeeding and to be switched from fluoxetine to a medication that would not increase the prolactin level. She did not require methotrexate treatment because her condition resolved rapidly after breastfeeding and fluoxetine were discontinued (Figure 2B).

Patient 2 

A 40-year-old woman with no history of breastfeeding who gave birth 4.5 years prior presented to her primary care provider with a painful breast lump and rash on the right breast of 2 months’ duration. Infectious mastitis was suspected; she was given cephalexin and clindamycin without improvement of symptoms.

Imaging
Mammography and ultrasonography were nondiagnostic.

Biopsy
Breast biopsy showed tissue with large expanses of histiocytes, neutrophils, lymphocytes, plasma cells, and multinucleated giant cells (Figure 3A). Many discrete granulomas were seen against this mixed inflammatory background, associated with focal fat necrosis (Figure 3B). Special stains were negative for microorganisms. Histologic findings were consistent with granulomatous mastitis.

On presentation to dermatology, the patient was worked up for a possible granulomatous etiology, which included a negative PPD, as well as a normal chest radiograph, serum Ca²⁺ and ACE levels, and ophthalmology examination. Review of symptoms (ROS),medical history, and medication review were unremarkable.

By exclusion, the patient was given a diagnosis of IGM and started on methotrexate (15 mg weekly) with folic acid (1 mg daily). The condition of the right breast improved within 4 weeks of starting methotrexate; however, methotrexate was increased to 30 mg weekly because of occasional flares. The patient remained on methotrexate without further IGM flares for 8 months compared to prior unremitting pain and drainage. She was then tapered from methotrexate over 6 weeks without additional flares.

 

 

Patient 3

A 27-year-old woman who gave birth 2 years prior and discontinued breastfeeding 6 weeks after delivery noted bilateral breast rashes for several months. The lesions were growing in size, tender, and draining. Her primary care provider suspected infectious mastitis and prescribed antibiotics, which were ineffective.

Biopsy
Breast core biopsy showed histologic findings similar to patients 1 and 2, including lobulocentric mixed inflammation, neutrophilic microabscesses, and scattered discrete granulomas. Microorganisms were not found using special stains. Breast cancer was ruled out, and granulomatous mastitis was diagnosed.

Referral to Dermatology
Two years earlier, the patient tested positive for latent tuberculosis and was prescribed a 9-month regimen of isoniazid. At the current presentation, she did not have symptoms of active tuberculosis on ROS (ie, no cough, hemoptysis, weight loss, night sweats); a chest radiograph was normal. Additionally, serum Ca²⁺ and ACE levels as well as an ophthalmology examination were normal, and she was not taking any medications known to increase the prolactin level.

The patient was started on methotrexate (12.5 mg weekly) and folic acid (1 mg daily). She had 1 IGM flare and was given a tapering regimen of prednisone. She received methotrexate for 14 months, tapered during the final 3 months. She has been off methotrexate for 3 years without IGM flares and appears to be in complete remission.

COMMENT

We report 3 cases of IGM, which contribute to the literature on possible presentations, causes, and conservative treatment of this rare connective-tissue disorder.

Differential Diagnosis

The time between recognition of symptoms and diagnosis and treatment of IGM often is prolonged because IGM can present similarly to other disorders, such as infection, breast cancer, tuberculosis, and sarcoidosis. Idiopathic granulomatous mastitis is a diagnosis of exclusion, made after obtaining evidence of granulomatous inflammation on breast biopsy and ruling out other granulomatous disorders, such as tuberculosis and sarcoidosis (Table 1).^3,4

Tuberculosis
A full ROS and a PPD test or T-SPOT.TB test can be helpful in ruling out tuberculosis; because anergy occurs in some patients, tuberculosis should be evaluated in the context of known immunosuppression or human immunodeficiency virus status, or in the case of miliary tuberculosis.

Chest radiography findings classically showing upper lobe infiltrates with cavities in active tuberculosis also should be sought.³ Ziehl-Neelsen staining of 2 sputum specimens, assessed by conventional light microscopy at the time of tissue biopsy has 64% sensitivity and 98% specificity for detecting Mycobacterium tuberculosis; auramine O staining, examined with light-emitting diode fluorescence microscopy, has 73% sensitivity and 93% specificity.⁵

Sarcoidosis
Because more than 90% of sarcoid patients have lung disease, a chest radiograph is used to screen for hilar lymphadenopathy.³ An elevated serum ACE level also can be helpful in diagnosis, but patients do not always have increased ACE, which can occur in other diseases, such as hyperthyroidism and miliary tuberculosis. Sarcoid granulomas can increase active vitamin D production, which in turn increases serum Ca²⁺ in 10% of sarcoid patients. Last, an ophthalmology evaluation should be obtained to rule out anterior or posterior uveitis that can occur in sarcoidosis and initially remain asymptomatic.³ Once these other causes of granulomatous inflammation have been ruled out, a diagnosis of IGM can be made.

Prolactinoma
Prolactinoma is an important cause of hyperprolactinemia that can be screened for based on ROS and the serum prolactin level. Prolactinoma can cause oligomenorrhea or amenorrhea and galactorrhea in 90% and 80% of premenopausal women, respectively, as well as erectile dysfunction and decreased libido in men. Infertility, headache, and visual impairment may be experienced in both sexes.⁴

A normal prolactin level is less than 25 μg/L; more than 25 μg/L but less than 100 μg/L usually is due to certain drugs (eTable),^6-11 estrogen, or idiopathic reasons; and more than 150 μg/L usually is due to prolactinoma.⁵ In many cases, removal of hyperprolactinemia-precipitating factors can resolve disease, as in patient 1. If symptoms continue or precipitating factors are absent, IGM symptom-based treatment should be administered.

Course and Management

Idiopathic granulomatous mastitis is self-limited and usually resolves within 2 years. Therefore, the goal of treatment is to suppress associated pain and drainage until the active inflammatory phase of IGM self-resolves. An established protocol for treating IGM does not exist, but common treatments include corticosteroids, methotrexate, and limited or wide surgical excision (Table 2).^12-16 Before beginning any of these treatments, IGM triggers, such as breastfeeding and drugs that induce hyperprolactinemia, should be removed.

It is important to consider which treatment option is best for limiting disease recurrence and adverse effects (AEs). Keep in mind that the available data are limited, as there are no randomized controlled trials looking at these treatments. Nevertheless, we recommend methotrexate as first line because it resolves granulomatous inflammation symptoms without invasive surgery, while limiting corticosteroid AEs.¹²

With or without concurrent use of corticosteroids, surgical excision typically is the mainstay of treatment. However, surgical excision of IGM lesions can be complicated by abscess formation, fistula, and chronic pyogenic secretions, in addition to a 5% to 50% rate of recurrence of disease.^12-14 Limited excision often is insufficient; therefore, wide local excision, in which negative margins around granulomatous inflammation are obtained, is the surgical modality of choice.¹⁴ Wide local excision can be disfiguring to the breast in young women affected by IGM, making it an undesirable treatment option.

Corticosteroids often have been used to treat IGM, but their efficacy is variable, symptoms can recur upon drug removal, and remarkable AEs can result from long-term use.¹² Additionally, corticosteroid therapy often is used in combination with excision, making it difficult to determine the extent to which corticosteroids or excision are more beneficial. In a prospective observational study, corticosteroid therapy alone resolved 80% of IGM symptoms after 159 days on average. After complete symptom resolution, 23% of patients had disease recurrence.⁹ Observed AEs included gastritis, weight gain, osteoporosis, glucose intolerance, and Cushing syndrome.^12,15

Methotrexate for IGM has not been reviewed in a randomized controlled trial; case reports have shown 83% symptom resolution, with 17% recurrence and limited long-term AEs.¹² Because the active phase of IGM can persist for 2 years, immunosuppressive therapy with limited AEs is necessary. Many AEs can occur when high-dose methotrexate is given for cancer treatment. Low-dose methotrexate has been extensively studied in long-term treatment of rheumatoid arthritis. Adverse effects may include gastrointestinal tract upset and hepatic dysfunction, which are limited when given with folic acid.

Regardless of folic acid cotreatment, stomatitis may occur. Women should use an effective method of birth control because severe birth defects may occur on even low-dose methotrexate.¹⁶

Compared to corticosteroid or surgical treatment, we recommend low-dose methotrexate therapy based on its high efficacy with limited AEs. An occasional mild flare of IGM symptoms with methotrexate is not unusual. If it occurs, corticosteroids can be added and tapered for as long as 2 weeks to speed up resolution of flares while reducing long-term AEs of corticosteroids.

Surgical excision can be performed in cases refractory to all systemic therapies.

CONCLUSION

Idiopathic granulomatous mastitis is a rare granulomatous breast disorder that can have a prolonged time to diagnosis, delaying proper treatment. Many cases self-resolve, but more severe cases can persist for a long period before adequate symptomatic treatment is achieved by methotrexate, corticosteroids, or surgical excision. Before using these therapies, it is important to identify and remove contributing factors, such as long-term breastfeeding and drugs that induce hyperprolactinemia. Improving the rate of IGM diagnosis and treatment would greatly benefit these patients. We report 1 case in which removal of possible precipitating IGM factors led to symptom resolution and 2 cases in which methotrexate was an effective IGM treatment that limited the need for invasive procedures and corticosteroid AEs.

Idiopathic granulomatous mastitis (IGM) is rare during pregnancy; it typically is seen in women of childbearing potential from 6 months to 6 years postpartum.¹ Because of a temporal association with breastfeeding, it is believed that hyperprolactinemia² or an immune response to local lobular secretions might play a role in pathogenesis. Early misdiagnosis as bacterial mastitis is common, prompting multiple antibiotic regimens. When antibiotics fail, patients are worked up for inflammatory breast cancer, given the nonhealing breast nodules. Mammography, ultrasonography, and fine-needle aspiration often are unable to rule out carcinoma, warranting excisional biopsies of nodules. The patient is then referred to rheumatology for potential sarcoidosis or to dermatology for IGM. In either case, the workup should be similar, but additional history focused on behavior and medications is essential in suspected IGM, given the association with hyperprolactinemia.

Because IGM is rare, there are no randomized, placebo-controlled trials of treatment efficacy. In many cases, patients undergo complete mastectomy, which is curative but may be psychologically and physically impactful in young women. In some cases, high-dose corticosteroids have been successful; however, because the IGM process can last longer than 2 years, patients treated in this manner are exposed to steroid morbidities.¹

We report 3 cases of IGM that add to the literature on possible contributing factors, clinical presentations, and treatments for this disease. We also demonstrate that appropriate trigger identification and steroid-sparing agents, specifically methotrexate, can be breast-saving as they can alleviate this debilitating condition, obviating the need for radical surgical intervention.

CASE REPORTS 

Patient 1

A 40-year-old woman with a 4-year history of breastfeeding noted a grape-sized nodule on the left breast that grew to the size of a grapefruit after 2 weeks. Ulceration and drainage periodically occurred, forming pink plaques along the lateral aspects of the breast after healing. Her primary care provider suspected infectious mastitis; she was given an oral antibiotic (cephalexin) and intravenous antibiotics without improvement.

Imaging
Subsequent magnetic resonance imaging revealed a large, irregular, enhancing mass within the outer left breast (6.5 cm at greatest dimension) with additional surrounding amorphous enhancement highly suspicious for malignancy. There also were multiple prominent left axillary lymph nodes, with the largest demonstrating a cortical thickness of 8 mm.

Biopsy
Core breast biopsy showed benign tissue with fat necrosis. Fine-needle aspiration revealed few benign ductal cells and rare histiocytes; because these findings were nondiagnostic and cancer was still a consideration, the patient underwent excisional biopsy.

Histologic sections of breast tissue showed extensive lobulocentric inflammation comprising histiocytes and lymphocytes, with neutrophils admixed and forming microabscesses (Figure 1A). Multinucleated giant cells and single-cell necrosis were seen, but true caseous necrosis was absent (Figure 1B). Duct spaces often contained inflammatory cells or secretions. Special stains for fungal and acid-fast bacterial microorganisms were negative.

Granulomatous lobular mastitis was diagnosed, and the patient was referred to dermatology. On presentation to dermatology, the left breast showed a 6-cm area of firm induration and overlying peau d’orange change to the epidermis (Figure 2A). Based on pathologic analysis, she was worked up for a possible granulomatous etiology. Negative purified protein derivative (tuberculin)(PPD) and a normal chest radiograph ruled out tuberculosis. Normal chest radiography, serum Ca²⁺ and angiotensin-converting enzyme (ACE) levels, and ophthalmology examination ruled out sarcoidosis.

The patient reported she continued breastfeeding her 4-year-old son. Additionally, she had been started on trazadone and buspirone for alcohol abuse recovery, then switched to and maintained on fluoxetine 1 year before developing these symptoms.

Buspirone, fluoxetine, and prolonged breastfeeding all contribute to hyperprolactinemia, a possible trigger of IGM. The patient was therefore advised to stop breastfeeding and to be switched from fluoxetine to a medication that would not increase the prolactin level. She did not require methotrexate treatment because her condition resolved rapidly after breastfeeding and fluoxetine were discontinued (Figure 2B).

Patient 2 

A 40-year-old woman with no history of breastfeeding who gave birth 4.5 years prior presented to her primary care provider with a painful breast lump and rash on the right breast of 2 months’ duration. Infectious mastitis was suspected; she was given cephalexin and clindamycin without improvement of symptoms.

Imaging
Mammography and ultrasonography were nondiagnostic.

Biopsy
Breast biopsy showed tissue with large expanses of histiocytes, neutrophils, lymphocytes, plasma cells, and multinucleated giant cells (Figure 3A). Many discrete granulomas were seen against this mixed inflammatory background, associated with focal fat necrosis (Figure 3B). Special stains were negative for microorganisms. Histologic findings were consistent with granulomatous mastitis.

On presentation to dermatology, the patient was worked up for a possible granulomatous etiology, which included a negative PPD, as well as a normal chest radiograph, serum Ca²⁺ and ACE levels, and ophthalmology examination. Review of symptoms (ROS),medical history, and medication review were unremarkable.

By exclusion, the patient was given a diagnosis of IGM and started on methotrexate (15 mg weekly) with folic acid (1 mg daily). The condition of the right breast improved within 4 weeks of starting methotrexate; however, methotrexate was increased to 30 mg weekly because of occasional flares. The patient remained on methotrexate without further IGM flares for 8 months compared to prior unremitting pain and drainage. She was then tapered from methotrexate over 6 weeks without additional flares.

 

 

Patient 3

A 27-year-old woman who gave birth 2 years prior and discontinued breastfeeding 6 weeks after delivery noted bilateral breast rashes for several months. The lesions were growing in size, tender, and draining. Her primary care provider suspected infectious mastitis and prescribed antibiotics, which were ineffective.

Biopsy
Breast core biopsy showed histologic findings similar to patients 1 and 2, including lobulocentric mixed inflammation, neutrophilic microabscesses, and scattered discrete granulomas. Microorganisms were not found using special stains. Breast cancer was ruled out, and granulomatous mastitis was diagnosed.

Referral to Dermatology
Two years earlier, the patient tested positive for latent tuberculosis and was prescribed a 9-month regimen of isoniazid. At the current presentation, she did not have symptoms of active tuberculosis on ROS (ie, no cough, hemoptysis, weight loss, night sweats); a chest radiograph was normal. Additionally, serum Ca²⁺ and ACE levels as well as an ophthalmology examination were normal, and she was not taking any medications known to increase the prolactin level.

The patient was started on methotrexate (12.5 mg weekly) and folic acid (1 mg daily). She had 1 IGM flare and was given a tapering regimen of prednisone. She received methotrexate for 14 months, tapered during the final 3 months. She has been off methotrexate for 3 years without IGM flares and appears to be in complete remission.

COMMENT

We report 3 cases of IGM, which contribute to the literature on possible presentations, causes, and conservative treatment of this rare connective-tissue disorder.

Differential Diagnosis

The time between recognition of symptoms and diagnosis and treatment of IGM often is prolonged because IGM can present similarly to other disorders, such as infection, breast cancer, tuberculosis, and sarcoidosis. Idiopathic granulomatous mastitis is a diagnosis of exclusion, made after obtaining evidence of granulomatous inflammation on breast biopsy and ruling out other granulomatous disorders, such as tuberculosis and sarcoidosis (Table 1).^3,4

Tuberculosis
A full ROS and a PPD test or T-SPOT.TB test can be helpful in ruling out tuberculosis; because anergy occurs in some patients, tuberculosis should be evaluated in the context of known immunosuppression or human immunodeficiency virus status, or in the case of miliary tuberculosis.

Chest radiography findings classically showing upper lobe infiltrates with cavities in active tuberculosis also should be sought.³ Ziehl-Neelsen staining of 2 sputum specimens, assessed by conventional light microscopy at the time of tissue biopsy has 64% sensitivity and 98% specificity for detecting Mycobacterium tuberculosis; auramine O staining, examined with light-emitting diode fluorescence microscopy, has 73% sensitivity and 93% specificity.⁵

Sarcoidosis
Because more than 90% of sarcoid patients have lung disease, a chest radiograph is used to screen for hilar lymphadenopathy.³ An elevated serum ACE level also can be helpful in diagnosis, but patients do not always have increased ACE, which can occur in other diseases, such as hyperthyroidism and miliary tuberculosis. Sarcoid granulomas can increase active vitamin D production, which in turn increases serum Ca²⁺ in 10% of sarcoid patients. Last, an ophthalmology evaluation should be obtained to rule out anterior or posterior uveitis that can occur in sarcoidosis and initially remain asymptomatic.³ Once these other causes of granulomatous inflammation have been ruled out, a diagnosis of IGM can be made.

Prolactinoma
Prolactinoma is an important cause of hyperprolactinemia that can be screened for based on ROS and the serum prolactin level. Prolactinoma can cause oligomenorrhea or amenorrhea and galactorrhea in 90% and 80% of premenopausal women, respectively, as well as erectile dysfunction and decreased libido in men. Infertility, headache, and visual impairment may be experienced in both sexes.⁴

A normal prolactin level is less than 25 μg/L; more than 25 μg/L but less than 100 μg/L usually is due to certain drugs (eTable),^6-11 estrogen, or idiopathic reasons; and more than 150 μg/L usually is due to prolactinoma.⁵ In many cases, removal of hyperprolactinemia-precipitating factors can resolve disease, as in patient 1. If symptoms continue or precipitating factors are absent, IGM symptom-based treatment should be administered.

Course and Management

Idiopathic granulomatous mastitis is self-limited and usually resolves within 2 years. Therefore, the goal of treatment is to suppress associated pain and drainage until the active inflammatory phase of IGM self-resolves. An established protocol for treating IGM does not exist, but common treatments include corticosteroids, methotrexate, and limited or wide surgical excision (Table 2).^12-16 Before beginning any of these treatments, IGM triggers, such as breastfeeding and drugs that induce hyperprolactinemia, should be removed.

It is important to consider which treatment option is best for limiting disease recurrence and adverse effects (AEs). Keep in mind that the available data are limited, as there are no randomized controlled trials looking at these treatments. Nevertheless, we recommend methotrexate as first line because it resolves granulomatous inflammation symptoms without invasive surgery, while limiting corticosteroid AEs.¹²

With or without concurrent use of corticosteroids, surgical excision typically is the mainstay of treatment. However, surgical excision of IGM lesions can be complicated by abscess formation, fistula, and chronic pyogenic secretions, in addition to a 5% to 50% rate of recurrence of disease.^12-14 Limited excision often is insufficient; therefore, wide local excision, in which negative margins around granulomatous inflammation are obtained, is the surgical modality of choice.¹⁴ Wide local excision can be disfiguring to the breast in young women affected by IGM, making it an undesirable treatment option.

Corticosteroids often have been used to treat IGM, but their efficacy is variable, symptoms can recur upon drug removal, and remarkable AEs can result from long-term use.¹² Additionally, corticosteroid therapy often is used in combination with excision, making it difficult to determine the extent to which corticosteroids or excision are more beneficial. In a prospective observational study, corticosteroid therapy alone resolved 80% of IGM symptoms after 159 days on average. After complete symptom resolution, 23% of patients had disease recurrence.⁹ Observed AEs included gastritis, weight gain, osteoporosis, glucose intolerance, and Cushing syndrome.^12,15

Methotrexate for IGM has not been reviewed in a randomized controlled trial; case reports have shown 83% symptom resolution, with 17% recurrence and limited long-term AEs.¹² Because the active phase of IGM can persist for 2 years, immunosuppressive therapy with limited AEs is necessary. Many AEs can occur when high-dose methotrexate is given for cancer treatment. Low-dose methotrexate has been extensively studied in long-term treatment of rheumatoid arthritis. Adverse effects may include gastrointestinal tract upset and hepatic dysfunction, which are limited when given with folic acid.

Regardless of folic acid cotreatment, stomatitis may occur. Women should use an effective method of birth control because severe birth defects may occur on even low-dose methotrexate.¹⁶

Compared to corticosteroid or surgical treatment, we recommend low-dose methotrexate therapy based on its high efficacy with limited AEs. An occasional mild flare of IGM symptoms with methotrexate is not unusual. If it occurs, corticosteroids can be added and tapered for as long as 2 weeks to speed up resolution of flares while reducing long-term AEs of corticosteroids.

Surgical excision can be performed in cases refractory to all systemic therapies.

CONCLUSION

Idiopathic granulomatous mastitis is a rare granulomatous breast disorder that can have a prolonged time to diagnosis, delaying proper treatment. Many cases self-resolve, but more severe cases can persist for a long period before adequate symptomatic treatment is achieved by methotrexate, corticosteroids, or surgical excision. Before using these therapies, it is important to identify and remove contributing factors, such as long-term breastfeeding and drugs that induce hyperprolactinemia. Improving the rate of IGM diagnosis and treatment would greatly benefit these patients. We report 1 case in which removal of possible precipitating IGM factors led to symptom resolution and 2 cases in which methotrexate was an effective IGM treatment that limited the need for invasive procedures and corticosteroid AEs.

Idiopathic granulomatous mastitis (IGM) is rare during pregnancy; it typically is seen in women of childbearing potential from 6 months to 6 years postpartum.¹ Because of a temporal association with breastfeeding, it is believed that hyperprolactinemia² or an immune response to local lobular secretions might play a role in pathogenesis. Early misdiagnosis as bacterial mastitis is common, prompting multiple antibiotic regimens. When antibiotics fail, patients are worked up for inflammatory breast cancer, given the nonhealing breast nodules. Mammography, ultrasonography, and fine-needle aspiration often are unable to rule out carcinoma, warranting excisional biopsies of nodules. The patient is then referred to rheumatology for potential sarcoidosis or to dermatology for IGM. In either case, the workup should be similar, but additional history focused on behavior and medications is essential in suspected IGM, given the association with hyperprolactinemia.

Because IGM is rare, there are no randomized, placebo-controlled trials of treatment efficacy. In many cases, patients undergo complete mastectomy, which is curative but may be psychologically and physically impactful in young women. In some cases, high-dose corticosteroids have been successful; however, because the IGM process can last longer than 2 years, patients treated in this manner are exposed to steroid morbidities.¹

We report 3 cases of IGM that add to the literature on possible contributing factors, clinical presentations, and treatments for this disease. We also demonstrate that appropriate trigger identification and steroid-sparing agents, specifically methotrexate, can be breast-saving as they can alleviate this debilitating condition, obviating the need for radical surgical intervention.

CASE REPORTS 

Patient 1

A 40-year-old woman with a 4-year history of breastfeeding noted a grape-sized nodule on the left breast that grew to the size of a grapefruit after 2 weeks. Ulceration and drainage periodically occurred, forming pink plaques along the lateral aspects of the breast after healing. Her primary care provider suspected infectious mastitis; she was given an oral antibiotic (cephalexin) and intravenous antibiotics without improvement.

Imaging
Subsequent magnetic resonance imaging revealed a large, irregular, enhancing mass within the outer left breast (6.5 cm at greatest dimension) with additional surrounding amorphous enhancement highly suspicious for malignancy. There also were multiple prominent left axillary lymph nodes, with the largest demonstrating a cortical thickness of 8 mm.

Biopsy
Core breast biopsy showed benign tissue with fat necrosis. Fine-needle aspiration revealed few benign ductal cells and rare histiocytes; because these findings were nondiagnostic and cancer was still a consideration, the patient underwent excisional biopsy.

Histologic sections of breast tissue showed extensive lobulocentric inflammation comprising histiocytes and lymphocytes, with neutrophils admixed and forming microabscesses (Figure 1A). Multinucleated giant cells and single-cell necrosis were seen, but true caseous necrosis was absent (Figure 1B). Duct spaces often contained inflammatory cells or secretions. Special stains for fungal and acid-fast bacterial microorganisms were negative.

Granulomatous lobular mastitis was diagnosed, and the patient was referred to dermatology. On presentation to dermatology, the left breast showed a 6-cm area of firm induration and overlying peau d’orange change to the epidermis (Figure 2A). Based on pathologic analysis, she was worked up for a possible granulomatous etiology. Negative purified protein derivative (tuberculin)(PPD) and a normal chest radiograph ruled out tuberculosis. Normal chest radiography, serum Ca²⁺ and angiotensin-converting enzyme (ACE) levels, and ophthalmology examination ruled out sarcoidosis.

The patient reported she continued breastfeeding her 4-year-old son. Additionally, she had been started on trazadone and buspirone for alcohol abuse recovery, then switched to and maintained on fluoxetine 1 year before developing these symptoms.

Buspirone, fluoxetine, and prolonged breastfeeding all contribute to hyperprolactinemia, a possible trigger of IGM. The patient was therefore advised to stop breastfeeding and to be switched from fluoxetine to a medication that would not increase the prolactin level. She did not require methotrexate treatment because her condition resolved rapidly after breastfeeding and fluoxetine were discontinued (Figure 2B).

Patient 2 

A 40-year-old woman with no history of breastfeeding who gave birth 4.5 years prior presented to her primary care provider with a painful breast lump and rash on the right breast of 2 months’ duration. Infectious mastitis was suspected; she was given cephalexin and clindamycin without improvement of symptoms.

Imaging
Mammography and ultrasonography were nondiagnostic.

Biopsy
Breast biopsy showed tissue with large expanses of histiocytes, neutrophils, lymphocytes, plasma cells, and multinucleated giant cells (Figure 3A). Many discrete granulomas were seen against this mixed inflammatory background, associated with focal fat necrosis (Figure 3B). Special stains were negative for microorganisms. Histologic findings were consistent with granulomatous mastitis.

On presentation to dermatology, the patient was worked up for a possible granulomatous etiology, which included a negative PPD, as well as a normal chest radiograph, serum Ca²⁺ and ACE levels, and ophthalmology examination. Review of symptoms (ROS),medical history, and medication review were unremarkable.

By exclusion, the patient was given a diagnosis of IGM and started on methotrexate (15 mg weekly) with folic acid (1 mg daily). The condition of the right breast improved within 4 weeks of starting methotrexate; however, methotrexate was increased to 30 mg weekly because of occasional flares. The patient remained on methotrexate without further IGM flares for 8 months compared to prior unremitting pain and drainage. She was then tapered from methotrexate over 6 weeks without additional flares.

 

 

Patient 3

A 27-year-old woman who gave birth 2 years prior and discontinued breastfeeding 6 weeks after delivery noted bilateral breast rashes for several months. The lesions were growing in size, tender, and draining. Her primary care provider suspected infectious mastitis and prescribed antibiotics, which were ineffective.

Biopsy
Breast core biopsy showed histologic findings similar to patients 1 and 2, including lobulocentric mixed inflammation, neutrophilic microabscesses, and scattered discrete granulomas. Microorganisms were not found using special stains. Breast cancer was ruled out, and granulomatous mastitis was diagnosed.

Referral to Dermatology
Two years earlier, the patient tested positive for latent tuberculosis and was prescribed a 9-month regimen of isoniazid. At the current presentation, she did not have symptoms of active tuberculosis on ROS (ie, no cough, hemoptysis, weight loss, night sweats); a chest radiograph was normal. Additionally, serum Ca²⁺ and ACE levels as well as an ophthalmology examination were normal, and she was not taking any medications known to increase the prolactin level.

The patient was started on methotrexate (12.5 mg weekly) and folic acid (1 mg daily). She had 1 IGM flare and was given a tapering regimen of prednisone. She received methotrexate for 14 months, tapered during the final 3 months. She has been off methotrexate for 3 years without IGM flares and appears to be in complete remission.

COMMENT

We report 3 cases of IGM, which contribute to the literature on possible presentations, causes, and conservative treatment of this rare connective-tissue disorder.

Differential Diagnosis

The time between recognition of symptoms and diagnosis and treatment of IGM often is prolonged because IGM can present similarly to other disorders, such as infection, breast cancer, tuberculosis, and sarcoidosis. Idiopathic granulomatous mastitis is a diagnosis of exclusion, made after obtaining evidence of granulomatous inflammation on breast biopsy and ruling out other granulomatous disorders, such as tuberculosis and sarcoidosis (Table 1).^3,4

Tuberculosis
A full ROS and a PPD test or T-SPOT.TB test can be helpful in ruling out tuberculosis; because anergy occurs in some patients, tuberculosis should be evaluated in the context of known immunosuppression or human immunodeficiency virus status, or in the case of miliary tuberculosis.

Chest radiography findings classically showing upper lobe infiltrates with cavities in active tuberculosis also should be sought.³ Ziehl-Neelsen staining of 2 sputum specimens, assessed by conventional light microscopy at the time of tissue biopsy has 64% sensitivity and 98% specificity for detecting Mycobacterium tuberculosis; auramine O staining, examined with light-emitting diode fluorescence microscopy, has 73% sensitivity and 93% specificity.⁵

Sarcoidosis
Because more than 90% of sarcoid patients have lung disease, a chest radiograph is used to screen for hilar lymphadenopathy.³ An elevated serum ACE level also can be helpful in diagnosis, but patients do not always have increased ACE, which can occur in other diseases, such as hyperthyroidism and miliary tuberculosis. Sarcoid granulomas can increase active vitamin D production, which in turn increases serum Ca²⁺ in 10% of sarcoid patients. Last, an ophthalmology evaluation should be obtained to rule out anterior or posterior uveitis that can occur in sarcoidosis and initially remain asymptomatic.³ Once these other causes of granulomatous inflammation have been ruled out, a diagnosis of IGM can be made.

Prolactinoma
Prolactinoma is an important cause of hyperprolactinemia that can be screened for based on ROS and the serum prolactin level. Prolactinoma can cause oligomenorrhea or amenorrhea and galactorrhea in 90% and 80% of premenopausal women, respectively, as well as erectile dysfunction and decreased libido in men. Infertility, headache, and visual impairment may be experienced in both sexes.⁴

A normal prolactin level is less than 25 μg/L; more than 25 μg/L but less than 100 μg/L usually is due to certain drugs (eTable),^6-11 estrogen, or idiopathic reasons; and more than 150 μg/L usually is due to prolactinoma.⁵ In many cases, removal of hyperprolactinemia-precipitating factors can resolve disease, as in patient 1. If symptoms continue or precipitating factors are absent, IGM symptom-based treatment should be administered.

Course and Management

Idiopathic granulomatous mastitis is self-limited and usually resolves within 2 years. Therefore, the goal of treatment is to suppress associated pain and drainage until the active inflammatory phase of IGM self-resolves. An established protocol for treating IGM does not exist, but common treatments include corticosteroids, methotrexate, and limited or wide surgical excision (Table 2).^12-16 Before beginning any of these treatments, IGM triggers, such as breastfeeding and drugs that induce hyperprolactinemia, should be removed.

It is important to consider which treatment option is best for limiting disease recurrence and adverse effects (AEs). Keep in mind that the available data are limited, as there are no randomized controlled trials looking at these treatments. Nevertheless, we recommend methotrexate as first line because it resolves granulomatous inflammation symptoms without invasive surgery, while limiting corticosteroid AEs.¹²

With or without concurrent use of corticosteroids, surgical excision typically is the mainstay of treatment. However, surgical excision of IGM lesions can be complicated by abscess formation, fistula, and chronic pyogenic secretions, in addition to a 5% to 50% rate of recurrence of disease.^12-14 Limited excision often is insufficient; therefore, wide local excision, in which negative margins around granulomatous inflammation are obtained, is the surgical modality of choice.¹⁴ Wide local excision can be disfiguring to the breast in young women affected by IGM, making it an undesirable treatment option.

Corticosteroids often have been used to treat IGM, but their efficacy is variable, symptoms can recur upon drug removal, and remarkable AEs can result from long-term use.¹² Additionally, corticosteroid therapy often is used in combination with excision, making it difficult to determine the extent to which corticosteroids or excision are more beneficial. In a prospective observational study, corticosteroid therapy alone resolved 80% of IGM symptoms after 159 days on average. After complete symptom resolution, 23% of patients had disease recurrence.⁹ Observed AEs included gastritis, weight gain, osteoporosis, glucose intolerance, and Cushing syndrome.^12,15

Methotrexate for IGM has not been reviewed in a randomized controlled trial; case reports have shown 83% symptom resolution, with 17% recurrence and limited long-term AEs.¹² Because the active phase of IGM can persist for 2 years, immunosuppressive therapy with limited AEs is necessary. Many AEs can occur when high-dose methotrexate is given for cancer treatment. Low-dose methotrexate has been extensively studied in long-term treatment of rheumatoid arthritis. Adverse effects may include gastrointestinal tract upset and hepatic dysfunction, which are limited when given with folic acid.

Regardless of folic acid cotreatment, stomatitis may occur. Women should use an effective method of birth control because severe birth defects may occur on even low-dose methotrexate.¹⁶

Compared to corticosteroid or surgical treatment, we recommend low-dose methotrexate therapy based on its high efficacy with limited AEs. An occasional mild flare of IGM symptoms with methotrexate is not unusual. If it occurs, corticosteroids can be added and tapered for as long as 2 weeks to speed up resolution of flares while reducing long-term AEs of corticosteroids.

Surgical excision can be performed in cases refractory to all systemic therapies.

CONCLUSION

Idiopathic granulomatous mastitis is a rare granulomatous breast disorder that can have a prolonged time to diagnosis, delaying proper treatment. Many cases self-resolve, but more severe cases can persist for a long period before adequate symptomatic treatment is achieved by methotrexate, corticosteroids, or surgical excision. Before using these therapies, it is important to identify and remove contributing factors, such as long-term breastfeeding and drugs that induce hyperprolactinemia. Improving the rate of IGM diagnosis and treatment would greatly benefit these patients. We report 1 case in which removal of possible precipitating IGM factors led to symptom resolution and 2 cases in which methotrexate was an effective IGM treatment that limited the need for invasive procedures and corticosteroid AEs.

In a national health care environment undergoing unprecedented transformation, the specialty of hospital medicine appears to be an island of relative stability, a conclusion that is supported by the principal findings from SHM’s 2018 State of Hospital Medicine (SoHM) report.

The report of hospitalist group practice characteristics, as well as other key data defining the field’s current status, that the Society of Hospital Medicine puts out every 2 years reveals that overall salaries for hospitalist physicians are up by 3.8% since 2016. Although productivity, as measured by work relative value units (RVUs), remained largely flat over the same period, financial support per full-time equivalent (FTE) physician position to hospitalist groups from their hospitals and health systems is up significantly.

Total support per FTE averaged $176,657 in 2018, 12% higher than in 2016, noted Leslie Flores, MHA, SFHM, of Nelson Flores Hospital Medicine Consultants, and a member of SHM’s Practice Analysis Committee, which oversees the biennial survey. Compensation and productivity data were collected by the Medical Group Management Association and licensed by SHM for inclusion in its report.

How do hospitalists use the SoHM report?

Dr. White called the 2018 SoHM report the “most representative and balanced sample to date” of hospitalist group practices, with some of the highest quality data, thanks to more robust participation in the survey by pediatric groups and improved distribution among hospitalist management companies and academic programs.

“Not that past reports had major flaws, but this version is more authoritative, reflecting an intentional effort by our Practice Analysis Committee to bring in more participants from key groups,” he said.

The biennial report has been around long enough to achieve brand recognition in the field as the most authoritative source of information regarding hospitalist practice, he added. “We worked hard this year to balance the participants, with more of our responses than in the past coming from multi-hospital groups, whether 4 to 5 sites, or 20 to 30.”

Surveys were conducted online in January and February of 2018 in response to invitations mailed and emailed to targeted hospital medicine group leaders. A total of 569 groups completed the survey, representing 8,889 hospitalist FTEs, approximately 16% of the total hospitalist workforce. Responses were presented in several categories, including by size of program, region and employment model. Groups that care for adults only represented 87.9% of the surveys, while groups that care for children only were 6.7% and groups that care for both adults and children were 5.4%.

Calls for more productivity

Roberta Himebaugh, MBA, SFHM, senior vice president of acute care services for the national hospitalist management company TeamHealth, and cochair of the SHM Practice Administrators Special Interest Group, said her company’s clients have traditionally asked for greater productivity from their hospitalist contracts as a way to decrease overall costs. Some markets are starting to see a change in that approach, she noted.

“Recently there’s been an increased focus on paying hospitalists to focus on quality rather than just productivity. Some of our clients are willing to pay for that, and we are trying to assign value to this non-billable time or adjust our productivity standards appropriately. I think hospitals definitely understand the value of non-billable services from hospitalists, but still will push us on the productivity targets,” Ms. Himebaugh said.

How is hospitalist practice evolving?

In addition to payment and productivity data, the SoHM report provides a current picture of the evolving state of hospitalist group practices. A key thread is how the work hospitalists are doing, and the way they do it, is changing, with new information about comanagement roles, dedicated admitters, night coverage, geographic rounding, and the like.

Making greater use of nurse practitioners and physician assistants (NPs/PAs), may be one way to change the flat productivity trends, Dr. Brown said. With a cost per RVU that’s roughly half that of a doctor’s, NPs/PAs could contribute to the bottom line. But he sees surprisingly large variation in how hospitalist groups are using them. Typically, they are deployed at a ratio of four doctors to one NP/PA, but that ratio could be two to one or even one to one, he said.

The predominant scheduling model of hospital medicine, 7 days on duty followed by 7 days off, has diminished somewhat in recent years. There appears to be some fluctuation and a gradual move away from 7 on/7 off toward some kind of variable approach, since the former may not be physically sustainable for the doctor over the long haul, Dr. Brown said. Some groups are experimenting with a combined approach.

“I think balancing workload with manpower has always been a challenge for our field. Maybe we should be working shorter shifts or fewer days and making sure our hospitalists aren’t ever sitting around idle,” he said. “And could we come in on nonclinical days to do administrative tasks? I think the solution is out there, but we haven’t created the algorithms to define that yet. If you could somehow use the data for volume, number of beds, nurse staffing, etc., by year and seasonally, you might be able to reliably predict census. This is about applying data hospitals already have in their electronic health records, but utilizing the data in ways that are more helpful.”

Dr. McIlraith added that a big driver of the future of hospital medicine will be the evolution of the EHR and the digitalization of health care, as hospitals learn how to leverage more of what’s in their EHRs. “The impact will grow for hospitalists through the creation and maturation of big data systems – and the learning that can be extracted from what’s contained in the electronic health record.”

Another important question for hospitalist groups is their model of backup scheduling, to make sure there is a replacement available if a scheduled doctor calls in sick or if demand is unexpectedly high.

“In today’s world, this is how we have traditionally managed unpredictability,” Dr. Brown said. “You don’t know when you will need it, but if you need it, you want it immediately. So how do you pay for it – only when the doctor comes in, or also an amount just for being on call?” Some groups pay for both, he said, others for neither.

“We are a group of 70 hospitalists, and if someone is sick you can’t just shut down the service,” said Dr. Chadha. “We are one of the few to use incentives for both, which could include a 1-week decrease in clinical shifts in exchange for 2 weeks of backup. We have times with 25% usage of backup number 1, and 10% usage of backup number 2,” he noted. “But the goal is for our hospitalists to have assurances that there is a backup system and that it works.”

The presence of nocturnists in hospitals continues to rise, with 76.1% of adults-only groups having nocturnists, 27.6% of children-only groups, and 68.2% of adults and children groups. Geographic or unit-based hospital assignments have grown to 36.4% of adult-only groups.

What are hospitalists’ other new roles?

“We have a large group of 50 doctors, with about 40 FTEs, and we are evolving from the traditional generalist role toward more subspecialty comanagement,” said Bryan Huang, MD, physician adviser and associate clinical professor in the division of hospital medicine at the University of California–San Diego. “Our hospitalists are asking what it means to be an academic hospitalist as our teaching roles have shrunk.”

Dr. Huang recently took on a new role as physician adviser for his hospital in such areas as utilization review, patient flow, and length of stay. “I’m spearheading a work group to address quality issues – all of which involve collaboration with other professionals. We also developed an admitting role here for a hospitalist whose sole role for the day is to admit patients.” Nationally up to 51.2% of hospitalist groups utilize a dedicated daytime admitter.

The report found that hospital services for which hospitalists are more likely to be attendings than consultants include GI/liver, 78.4%; palliative care, 77.3%; neurology/stroke, 73.6%; oncology, 67.8%; cardiology, 56.9%; and critical care, 50.7%. Conditions where hospitalists are more likely to consult rather than admit and attend include neurosurgery, orthopedics, general surgery, cardiovascular surgery, and other surgical subspecialties.

Other hospital services routinely provided by adult-only hospitalists include care of patients in an ICU setting (62.7%); primary responsibility for observation units (54.6%); primary clinical responsibility for rapid response teams (48.8%); primary responsibility for code blue or cardiac arrest teams (43.8%); nighttime admissions or tuck-in services (33.9%); and medical procedures (31.5%). For pediatric hospital medicine groups, care of healthy newborns and medical procedures were among the most common services provided, while for hospitalists serving adults and children, rapid response teams, ICUs, and specialty units were most common.

New models of payment for health care

As the larger health care system is being transformed by new payment models and benefit structures, including accountable care organizations (ACOs), value-based purchasing, bundled payments, and other forms of population-based coverage – which is described as a volume-to-value shift in health care – how are these new models affecting hospitalists?

Observers say penetration of these new models varies widely by locality but they haven’t had much direct impact on hospitalists’ practices – at least not yet. However, as hospitals and health systems find themselves needing to learn new ways to invest their resources differently in response to these trends, what matters to the hospital should be of great importance to the hospitalist group.

“I haven’t seen a lot of dramatic changes in how hospitalists engage with value-based purchasing,” Dr. White said. “If we know that someone is part of an ACO, the instinctual – and right – response is to treat them like any other patient. But we still need to be committed to not waste resources.”

Hospitalists are the best people to understand the intricacies of how the health care system works under value-based approaches, Dr. Huang said. “That’s why so many hospitalists have taken leadership positions in their hospitals. I think all of this translates to the practical, day-to-day work of hospitalists, reflected in our focus on readmissions and length of stay.”

Dr. Williams said the health care system still hasn’t turned the corner from fee-for-service to value-based purchasing. “It still represents a tiny fraction of the income of hospitalists. Hospitals still have to focus on the bottom line, as fee-for-service reimbursement for hospitalized patients continues to get squeezed, and ACOs aren’t exactly paying premium rates either. Ask almost any hospital CEO what drives their bottom line today and the answer is volume – along with optimizing productivity. Pretty much every place I look, the future does not look terribly rosy for hospitals.”

Ms. Himebaugh said she is bullish on hospital medicine, in the sense that it’s unlikely to go away anytime soon. “Hospitalists are needed and provide value. But I don’t think we have devised the right model yet. I’m not sure our current model is sustainable. We need to find new models we can afford that don’t require squeezing our providers.”

For more information about the 2018 State of Hospital Medicine Report, contact SHM’s Practice Management Department at: [email protected] or call 800-843-3360. See also: https://www.hospitalmedicine.org/practice-management/shms-state-of-hospital-medicine/.

In a national health care environment undergoing unprecedented transformation, the specialty of hospital medicine appears to be an island of relative stability, a conclusion that is supported by the principal findings from SHM’s 2018 State of Hospital Medicine (SoHM) report.

The report of hospitalist group practice characteristics, as well as other key data defining the field’s current status, that the Society of Hospital Medicine puts out every 2 years reveals that overall salaries for hospitalist physicians are up by 3.8% since 2016. Although productivity, as measured by work relative value units (RVUs), remained largely flat over the same period, financial support per full-time equivalent (FTE) physician position to hospitalist groups from their hospitals and health systems is up significantly.

Total support per FTE averaged $176,657 in 2018, 12% higher than in 2016, noted Leslie Flores, MHA, SFHM, of Nelson Flores Hospital Medicine Consultants, and a member of SHM’s Practice Analysis Committee, which oversees the biennial survey. Compensation and productivity data were collected by the Medical Group Management Association and licensed by SHM for inclusion in its report.

How do hospitalists use the SoHM report?

Dr. White called the 2018 SoHM report the “most representative and balanced sample to date” of hospitalist group practices, with some of the highest quality data, thanks to more robust participation in the survey by pediatric groups and improved distribution among hospitalist management companies and academic programs.

“Not that past reports had major flaws, but this version is more authoritative, reflecting an intentional effort by our Practice Analysis Committee to bring in more participants from key groups,” he said.

The biennial report has been around long enough to achieve brand recognition in the field as the most authoritative source of information regarding hospitalist practice, he added. “We worked hard this year to balance the participants, with more of our responses than in the past coming from multi-hospital groups, whether 4 to 5 sites, or 20 to 30.”

Surveys were conducted online in January and February of 2018 in response to invitations mailed and emailed to targeted hospital medicine group leaders. A total of 569 groups completed the survey, representing 8,889 hospitalist FTEs, approximately 16% of the total hospitalist workforce. Responses were presented in several categories, including by size of program, region and employment model. Groups that care for adults only represented 87.9% of the surveys, while groups that care for children only were 6.7% and groups that care for both adults and children were 5.4%.

Calls for more productivity

Roberta Himebaugh, MBA, SFHM, senior vice president of acute care services for the national hospitalist management company TeamHealth, and cochair of the SHM Practice Administrators Special Interest Group, said her company’s clients have traditionally asked for greater productivity from their hospitalist contracts as a way to decrease overall costs. Some markets are starting to see a change in that approach, she noted.

“Recently there’s been an increased focus on paying hospitalists to focus on quality rather than just productivity. Some of our clients are willing to pay for that, and we are trying to assign value to this non-billable time or adjust our productivity standards appropriately. I think hospitals definitely understand the value of non-billable services from hospitalists, but still will push us on the productivity targets,” Ms. Himebaugh said.

How is hospitalist practice evolving?

In addition to payment and productivity data, the SoHM report provides a current picture of the evolving state of hospitalist group practices. A key thread is how the work hospitalists are doing, and the way they do it, is changing, with new information about comanagement roles, dedicated admitters, night coverage, geographic rounding, and the like.

Making greater use of nurse practitioners and physician assistants (NPs/PAs), may be one way to change the flat productivity trends, Dr. Brown said. With a cost per RVU that’s roughly half that of a doctor’s, NPs/PAs could contribute to the bottom line. But he sees surprisingly large variation in how hospitalist groups are using them. Typically, they are deployed at a ratio of four doctors to one NP/PA, but that ratio could be two to one or even one to one, he said.

The predominant scheduling model of hospital medicine, 7 days on duty followed by 7 days off, has diminished somewhat in recent years. There appears to be some fluctuation and a gradual move away from 7 on/7 off toward some kind of variable approach, since the former may not be physically sustainable for the doctor over the long haul, Dr. Brown said. Some groups are experimenting with a combined approach.

“I think balancing workload with manpower has always been a challenge for our field. Maybe we should be working shorter shifts or fewer days and making sure our hospitalists aren’t ever sitting around idle,” he said. “And could we come in on nonclinical days to do administrative tasks? I think the solution is out there, but we haven’t created the algorithms to define that yet. If you could somehow use the data for volume, number of beds, nurse staffing, etc., by year and seasonally, you might be able to reliably predict census. This is about applying data hospitals already have in their electronic health records, but utilizing the data in ways that are more helpful.”

Dr. McIlraith added that a big driver of the future of hospital medicine will be the evolution of the EHR and the digitalization of health care, as hospitals learn how to leverage more of what’s in their EHRs. “The impact will grow for hospitalists through the creation and maturation of big data systems – and the learning that can be extracted from what’s contained in the electronic health record.”

Another important question for hospitalist groups is their model of backup scheduling, to make sure there is a replacement available if a scheduled doctor calls in sick or if demand is unexpectedly high.

“In today’s world, this is how we have traditionally managed unpredictability,” Dr. Brown said. “You don’t know when you will need it, but if you need it, you want it immediately. So how do you pay for it – only when the doctor comes in, or also an amount just for being on call?” Some groups pay for both, he said, others for neither.

“We are a group of 70 hospitalists, and if someone is sick you can’t just shut down the service,” said Dr. Chadha. “We are one of the few to use incentives for both, which could include a 1-week decrease in clinical shifts in exchange for 2 weeks of backup. We have times with 25% usage of backup number 1, and 10% usage of backup number 2,” he noted. “But the goal is for our hospitalists to have assurances that there is a backup system and that it works.”

The presence of nocturnists in hospitals continues to rise, with 76.1% of adults-only groups having nocturnists, 27.6% of children-only groups, and 68.2% of adults and children groups. Geographic or unit-based hospital assignments have grown to 36.4% of adult-only groups.

What are hospitalists’ other new roles?

“We have a large group of 50 doctors, with about 40 FTEs, and we are evolving from the traditional generalist role toward more subspecialty comanagement,” said Bryan Huang, MD, physician adviser and associate clinical professor in the division of hospital medicine at the University of California–San Diego. “Our hospitalists are asking what it means to be an academic hospitalist as our teaching roles have shrunk.”

Dr. Huang recently took on a new role as physician adviser for his hospital in such areas as utilization review, patient flow, and length of stay. “I’m spearheading a work group to address quality issues – all of which involve collaboration with other professionals. We also developed an admitting role here for a hospitalist whose sole role for the day is to admit patients.” Nationally up to 51.2% of hospitalist groups utilize a dedicated daytime admitter.

The report found that hospital services for which hospitalists are more likely to be attendings than consultants include GI/liver, 78.4%; palliative care, 77.3%; neurology/stroke, 73.6%; oncology, 67.8%; cardiology, 56.9%; and critical care, 50.7%. Conditions where hospitalists are more likely to consult rather than admit and attend include neurosurgery, orthopedics, general surgery, cardiovascular surgery, and other surgical subspecialties.

Other hospital services routinely provided by adult-only hospitalists include care of patients in an ICU setting (62.7%); primary responsibility for observation units (54.6%); primary clinical responsibility for rapid response teams (48.8%); primary responsibility for code blue or cardiac arrest teams (43.8%); nighttime admissions or tuck-in services (33.9%); and medical procedures (31.5%). For pediatric hospital medicine groups, care of healthy newborns and medical procedures were among the most common services provided, while for hospitalists serving adults and children, rapid response teams, ICUs, and specialty units were most common.

New models of payment for health care

As the larger health care system is being transformed by new payment models and benefit structures, including accountable care organizations (ACOs), value-based purchasing, bundled payments, and other forms of population-based coverage – which is described as a volume-to-value shift in health care – how are these new models affecting hospitalists?

Observers say penetration of these new models varies widely by locality but they haven’t had much direct impact on hospitalists’ practices – at least not yet. However, as hospitals and health systems find themselves needing to learn new ways to invest their resources differently in response to these trends, what matters to the hospital should be of great importance to the hospitalist group.

“I haven’t seen a lot of dramatic changes in how hospitalists engage with value-based purchasing,” Dr. White said. “If we know that someone is part of an ACO, the instinctual – and right – response is to treat them like any other patient. But we still need to be committed to not waste resources.”

Hospitalists are the best people to understand the intricacies of how the health care system works under value-based approaches, Dr. Huang said. “That’s why so many hospitalists have taken leadership positions in their hospitals. I think all of this translates to the practical, day-to-day work of hospitalists, reflected in our focus on readmissions and length of stay.”

Dr. Williams said the health care system still hasn’t turned the corner from fee-for-service to value-based purchasing. “It still represents a tiny fraction of the income of hospitalists. Hospitals still have to focus on the bottom line, as fee-for-service reimbursement for hospitalized patients continues to get squeezed, and ACOs aren’t exactly paying premium rates either. Ask almost any hospital CEO what drives their bottom line today and the answer is volume – along with optimizing productivity. Pretty much every place I look, the future does not look terribly rosy for hospitals.”

Ms. Himebaugh said she is bullish on hospital medicine, in the sense that it’s unlikely to go away anytime soon. “Hospitalists are needed and provide value. But I don’t think we have devised the right model yet. I’m not sure our current model is sustainable. We need to find new models we can afford that don’t require squeezing our providers.”

For more information about the 2018 State of Hospital Medicine Report, contact SHM’s Practice Management Department at: [email protected] or call 800-843-3360. See also: https://www.hospitalmedicine.org/practice-management/shms-state-of-hospital-medicine/.

In a national health care environment undergoing unprecedented transformation, the specialty of hospital medicine appears to be an island of relative stability, a conclusion that is supported by the principal findings from SHM’s 2018 State of Hospital Medicine (SoHM) report.

The report of hospitalist group practice characteristics, as well as other key data defining the field’s current status, that the Society of Hospital Medicine puts out every 2 years reveals that overall salaries for hospitalist physicians are up by 3.8% since 2016. Although productivity, as measured by work relative value units (RVUs), remained largely flat over the same period, financial support per full-time equivalent (FTE) physician position to hospitalist groups from their hospitals and health systems is up significantly.

Total support per FTE averaged $176,657 in 2018, 12% higher than in 2016, noted Leslie Flores, MHA, SFHM, of Nelson Flores Hospital Medicine Consultants, and a member of SHM’s Practice Analysis Committee, which oversees the biennial survey. Compensation and productivity data were collected by the Medical Group Management Association and licensed by SHM for inclusion in its report.

How do hospitalists use the SoHM report?

Dr. White called the 2018 SoHM report the “most representative and balanced sample to date” of hospitalist group practices, with some of the highest quality data, thanks to more robust participation in the survey by pediatric groups and improved distribution among hospitalist management companies and academic programs.

“Not that past reports had major flaws, but this version is more authoritative, reflecting an intentional effort by our Practice Analysis Committee to bring in more participants from key groups,” he said.

The biennial report has been around long enough to achieve brand recognition in the field as the most authoritative source of information regarding hospitalist practice, he added. “We worked hard this year to balance the participants, with more of our responses than in the past coming from multi-hospital groups, whether 4 to 5 sites, or 20 to 30.”

Surveys were conducted online in January and February of 2018 in response to invitations mailed and emailed to targeted hospital medicine group leaders. A total of 569 groups completed the survey, representing 8,889 hospitalist FTEs, approximately 16% of the total hospitalist workforce. Responses were presented in several categories, including by size of program, region and employment model. Groups that care for adults only represented 87.9% of the surveys, while groups that care for children only were 6.7% and groups that care for both adults and children were 5.4%.

Calls for more productivity

Roberta Himebaugh, MBA, SFHM, senior vice president of acute care services for the national hospitalist management company TeamHealth, and cochair of the SHM Practice Administrators Special Interest Group, said her company’s clients have traditionally asked for greater productivity from their hospitalist contracts as a way to decrease overall costs. Some markets are starting to see a change in that approach, she noted.

“Recently there’s been an increased focus on paying hospitalists to focus on quality rather than just productivity. Some of our clients are willing to pay for that, and we are trying to assign value to this non-billable time or adjust our productivity standards appropriately. I think hospitals definitely understand the value of non-billable services from hospitalists, but still will push us on the productivity targets,” Ms. Himebaugh said.

How is hospitalist practice evolving?

In addition to payment and productivity data, the SoHM report provides a current picture of the evolving state of hospitalist group practices. A key thread is how the work hospitalists are doing, and the way they do it, is changing, with new information about comanagement roles, dedicated admitters, night coverage, geographic rounding, and the like.

Making greater use of nurse practitioners and physician assistants (NPs/PAs), may be one way to change the flat productivity trends, Dr. Brown said. With a cost per RVU that’s roughly half that of a doctor’s, NPs/PAs could contribute to the bottom line. But he sees surprisingly large variation in how hospitalist groups are using them. Typically, they are deployed at a ratio of four doctors to one NP/PA, but that ratio could be two to one or even one to one, he said.

The predominant scheduling model of hospital medicine, 7 days on duty followed by 7 days off, has diminished somewhat in recent years. There appears to be some fluctuation and a gradual move away from 7 on/7 off toward some kind of variable approach, since the former may not be physically sustainable for the doctor over the long haul, Dr. Brown said. Some groups are experimenting with a combined approach.

“I think balancing workload with manpower has always been a challenge for our field. Maybe we should be working shorter shifts or fewer days and making sure our hospitalists aren’t ever sitting around idle,” he said. “And could we come in on nonclinical days to do administrative tasks? I think the solution is out there, but we haven’t created the algorithms to define that yet. If you could somehow use the data for volume, number of beds, nurse staffing, etc., by year and seasonally, you might be able to reliably predict census. This is about applying data hospitals already have in their electronic health records, but utilizing the data in ways that are more helpful.”

Dr. McIlraith added that a big driver of the future of hospital medicine will be the evolution of the EHR and the digitalization of health care, as hospitals learn how to leverage more of what’s in their EHRs. “The impact will grow for hospitalists through the creation and maturation of big data systems – and the learning that can be extracted from what’s contained in the electronic health record.”

Another important question for hospitalist groups is their model of backup scheduling, to make sure there is a replacement available if a scheduled doctor calls in sick or if demand is unexpectedly high.

“In today’s world, this is how we have traditionally managed unpredictability,” Dr. Brown said. “You don’t know when you will need it, but if you need it, you want it immediately. So how do you pay for it – only when the doctor comes in, or also an amount just for being on call?” Some groups pay for both, he said, others for neither.

“We are a group of 70 hospitalists, and if someone is sick you can’t just shut down the service,” said Dr. Chadha. “We are one of the few to use incentives for both, which could include a 1-week decrease in clinical shifts in exchange for 2 weeks of backup. We have times with 25% usage of backup number 1, and 10% usage of backup number 2,” he noted. “But the goal is for our hospitalists to have assurances that there is a backup system and that it works.”

The presence of nocturnists in hospitals continues to rise, with 76.1% of adults-only groups having nocturnists, 27.6% of children-only groups, and 68.2% of adults and children groups. Geographic or unit-based hospital assignments have grown to 36.4% of adult-only groups.

What are hospitalists’ other new roles?

“We have a large group of 50 doctors, with about 40 FTEs, and we are evolving from the traditional generalist role toward more subspecialty comanagement,” said Bryan Huang, MD, physician adviser and associate clinical professor in the division of hospital medicine at the University of California–San Diego. “Our hospitalists are asking what it means to be an academic hospitalist as our teaching roles have shrunk.”

Dr. Huang recently took on a new role as physician adviser for his hospital in such areas as utilization review, patient flow, and length of stay. “I’m spearheading a work group to address quality issues – all of which involve collaboration with other professionals. We also developed an admitting role here for a hospitalist whose sole role for the day is to admit patients.” Nationally up to 51.2% of hospitalist groups utilize a dedicated daytime admitter.

The report found that hospital services for which hospitalists are more likely to be attendings than consultants include GI/liver, 78.4%; palliative care, 77.3%; neurology/stroke, 73.6%; oncology, 67.8%; cardiology, 56.9%; and critical care, 50.7%. Conditions where hospitalists are more likely to consult rather than admit and attend include neurosurgery, orthopedics, general surgery, cardiovascular surgery, and other surgical subspecialties.

Other hospital services routinely provided by adult-only hospitalists include care of patients in an ICU setting (62.7%); primary responsibility for observation units (54.6%); primary clinical responsibility for rapid response teams (48.8%); primary responsibility for code blue or cardiac arrest teams (43.8%); nighttime admissions or tuck-in services (33.9%); and medical procedures (31.5%). For pediatric hospital medicine groups, care of healthy newborns and medical procedures were among the most common services provided, while for hospitalists serving adults and children, rapid response teams, ICUs, and specialty units were most common.

New models of payment for health care

As the larger health care system is being transformed by new payment models and benefit structures, including accountable care organizations (ACOs), value-based purchasing, bundled payments, and other forms of population-based coverage – which is described as a volume-to-value shift in health care – how are these new models affecting hospitalists?

Observers say penetration of these new models varies widely by locality but they haven’t had much direct impact on hospitalists’ practices – at least not yet. However, as hospitals and health systems find themselves needing to learn new ways to invest their resources differently in response to these trends, what matters to the hospital should be of great importance to the hospitalist group.

“I haven’t seen a lot of dramatic changes in how hospitalists engage with value-based purchasing,” Dr. White said. “If we know that someone is part of an ACO, the instinctual – and right – response is to treat them like any other patient. But we still need to be committed to not waste resources.”

Hospitalists are the best people to understand the intricacies of how the health care system works under value-based approaches, Dr. Huang said. “That’s why so many hospitalists have taken leadership positions in their hospitals. I think all of this translates to the practical, day-to-day work of hospitalists, reflected in our focus on readmissions and length of stay.”

Dr. Williams said the health care system still hasn’t turned the corner from fee-for-service to value-based purchasing. “It still represents a tiny fraction of the income of hospitalists. Hospitals still have to focus on the bottom line, as fee-for-service reimbursement for hospitalized patients continues to get squeezed, and ACOs aren’t exactly paying premium rates either. Ask almost any hospital CEO what drives their bottom line today and the answer is volume – along with optimizing productivity. Pretty much every place I look, the future does not look terribly rosy for hospitals.”

Ms. Himebaugh said she is bullish on hospital medicine, in the sense that it’s unlikely to go away anytime soon. “Hospitalists are needed and provide value. But I don’t think we have devised the right model yet. I’m not sure our current model is sustainable. We need to find new models we can afford that don’t require squeezing our providers.”

For more information about the 2018 State of Hospital Medicine Report, contact SHM’s Practice Management Department at: [email protected] or call 800-843-3360. See also: https://www.hospitalmedicine.org/practice-management/shms-state-of-hospital-medicine/.

A Medicare program aimed at lowering readmissions to hospitals could be having an adverse effect on mortality.

Copyright Kimberly Pack/Thinkstock

Results from a retrospective cohort study of hospitalizations for heart failure, acute myocardial infarction, and pneumonia among Medicare beneficiaries aged 65 years and older between April 1, 2005 and March 31, 2015 (covering the period before and after the Medicare Hospital Readmissions Reduction Program was announced in April 2010 and implemented in October 2012) found a significant increase in 30-day post discharge mortality among heart failure and pneumonia patients.

“Most concerning, however, is the possibility that the relationship between the HRRP and postdischarge mortality for heart failure and pneumonia is causal, indicating that the HRRP led to changes in quality of care that adversely affected patients,” Rishi Wadhera, MD, Harvard Medical School, Boston, and his colleagues wrote in a report published Dec. 25, 2018, in JAMA.

They looked at 8.3 million hospitalizations for heart failure, acute MI, and pneumonia, among whom 7.9 million were alive at the time of discharge. There were roughly 270,000 deaths within 30 days of discharge for heart failure; 128,000 for acute MI; and 246,000 for pneumonia.

To examine trends, the timing was divided into four periods: two prior to the announcement of the HRRP (April 2005–September 2007 and October 2007–March 2010); a third covering the time when the HRRP was announced (April 2010–September 2012); and the fourth when HRRP was implemented (October 2012–March 2015).

They found that among patients discharged with heart failure, 30-day mortality was rising even before the announcement of the HRRP, by 0.27% from the first period to the second period. That baseline trend continued when the HRRP was announced, by 0.49%, from second period to third. The difference in change between those periods was 0.22%. After implementation, 30-day mortality increased by 0.52%, with a difference in change from the third period of 0.25%. Both changes were statistically significant.

Among pneumonia patients, postdischarge mortality was stable before HRRP, but significantly increased after HRRP announcement, by 0.26%, with a difference in change from the second period to the third period of 0.22%. After implementation, the 30-day postdischarge mortality was 0.44%, with a significant difference in change of 0.40%.

Acute MI was a different story. Postdischarge mortality decreased significantly after the implementation of the HRRP, by 0.22%. The difference in change was –0.26%.

The authors suggested that “some hospitals may have focused more resources and efforts on reducing or avoiding readmissions than on prioritizing survival.” They add that the increases in heart failure morbidity could be related to patients with more severe heart conditions.

They noted that “although hospitals that reduce readmissions also appear to reduce mortality, this hospital-level concordance does not reflect the change in readmissions and mortality at the level of the patient population, which is arguably of greater importance to individual patients and to public health.”

Further research is needed to understand whether the increase in 30-day postdischarge mortality is a result of the HRRP, the authors concluded.

[email protected]

SOURCE: Wadhera R et al. JAMA. 2018 Dec 25. doi: 10.1001/jama.2018.19232.

A Medicare program aimed at lowering readmissions to hospitals could be having an adverse effect on mortality.

Copyright Kimberly Pack/Thinkstock

Results from a retrospective cohort study of hospitalizations for heart failure, acute myocardial infarction, and pneumonia among Medicare beneficiaries aged 65 years and older between April 1, 2005 and March 31, 2015 (covering the period before and after the Medicare Hospital Readmissions Reduction Program was announced in April 2010 and implemented in October 2012) found a significant increase in 30-day post discharge mortality among heart failure and pneumonia patients.

“Most concerning, however, is the possibility that the relationship between the HRRP and postdischarge mortality for heart failure and pneumonia is causal, indicating that the HRRP led to changes in quality of care that adversely affected patients,” Rishi Wadhera, MD, Harvard Medical School, Boston, and his colleagues wrote in a report published Dec. 25, 2018, in JAMA.

They looked at 8.3 million hospitalizations for heart failure, acute MI, and pneumonia, among whom 7.9 million were alive at the time of discharge. There were roughly 270,000 deaths within 30 days of discharge for heart failure; 128,000 for acute MI; and 246,000 for pneumonia.

To examine trends, the timing was divided into four periods: two prior to the announcement of the HRRP (April 2005–September 2007 and October 2007–March 2010); a third covering the time when the HRRP was announced (April 2010–September 2012); and the fourth when HRRP was implemented (October 2012–March 2015).

They found that among patients discharged with heart failure, 30-day mortality was rising even before the announcement of the HRRP, by 0.27% from the first period to the second period. That baseline trend continued when the HRRP was announced, by 0.49%, from second period to third. The difference in change between those periods was 0.22%. After implementation, 30-day mortality increased by 0.52%, with a difference in change from the third period of 0.25%. Both changes were statistically significant.

Among pneumonia patients, postdischarge mortality was stable before HRRP, but significantly increased after HRRP announcement, by 0.26%, with a difference in change from the second period to the third period of 0.22%. After implementation, the 30-day postdischarge mortality was 0.44%, with a significant difference in change of 0.40%.

Acute MI was a different story. Postdischarge mortality decreased significantly after the implementation of the HRRP, by 0.22%. The difference in change was –0.26%.

The authors suggested that “some hospitals may have focused more resources and efforts on reducing or avoiding readmissions than on prioritizing survival.” They add that the increases in heart failure morbidity could be related to patients with more severe heart conditions.

They noted that “although hospitals that reduce readmissions also appear to reduce mortality, this hospital-level concordance does not reflect the change in readmissions and mortality at the level of the patient population, which is arguably of greater importance to individual patients and to public health.”

Further research is needed to understand whether the increase in 30-day postdischarge mortality is a result of the HRRP, the authors concluded.

[email protected]

SOURCE: Wadhera R et al. JAMA. 2018 Dec 25. doi: 10.1001/jama.2018.19232.

A Medicare program aimed at lowering readmissions to hospitals could be having an adverse effect on mortality.

Copyright Kimberly Pack/Thinkstock

Results from a retrospective cohort study of hospitalizations for heart failure, acute myocardial infarction, and pneumonia among Medicare beneficiaries aged 65 years and older between April 1, 2005 and March 31, 2015 (covering the period before and after the Medicare Hospital Readmissions Reduction Program was announced in April 2010 and implemented in October 2012) found a significant increase in 30-day post discharge mortality among heart failure and pneumonia patients.

“Most concerning, however, is the possibility that the relationship between the HRRP and postdischarge mortality for heart failure and pneumonia is causal, indicating that the HRRP led to changes in quality of care that adversely affected patients,” Rishi Wadhera, MD, Harvard Medical School, Boston, and his colleagues wrote in a report published Dec. 25, 2018, in JAMA.

They looked at 8.3 million hospitalizations for heart failure, acute MI, and pneumonia, among whom 7.9 million were alive at the time of discharge. There were roughly 270,000 deaths within 30 days of discharge for heart failure; 128,000 for acute MI; and 246,000 for pneumonia.

To examine trends, the timing was divided into four periods: two prior to the announcement of the HRRP (April 2005–September 2007 and October 2007–March 2010); a third covering the time when the HRRP was announced (April 2010–September 2012); and the fourth when HRRP was implemented (October 2012–March 2015).

They found that among patients discharged with heart failure, 30-day mortality was rising even before the announcement of the HRRP, by 0.27% from the first period to the second period. That baseline trend continued when the HRRP was announced, by 0.49%, from second period to third. The difference in change between those periods was 0.22%. After implementation, 30-day mortality increased by 0.52%, with a difference in change from the third period of 0.25%. Both changes were statistically significant.

Among pneumonia patients, postdischarge mortality was stable before HRRP, but significantly increased after HRRP announcement, by 0.26%, with a difference in change from the second period to the third period of 0.22%. After implementation, the 30-day postdischarge mortality was 0.44%, with a significant difference in change of 0.40%.

Acute MI was a different story. Postdischarge mortality decreased significantly after the implementation of the HRRP, by 0.22%. The difference in change was –0.26%.

The authors suggested that “some hospitals may have focused more resources and efforts on reducing or avoiding readmissions than on prioritizing survival.” They add that the increases in heart failure morbidity could be related to patients with more severe heart conditions.

They noted that “although hospitals that reduce readmissions also appear to reduce mortality, this hospital-level concordance does not reflect the change in readmissions and mortality at the level of the patient population, which is arguably of greater importance to individual patients and to public health.”

Further research is needed to understand whether the increase in 30-day postdischarge mortality is a result of the HRRP, the authors concluded.

[email protected]

SOURCE: Wadhera R et al. JAMA. 2018 Dec 25. doi: 10.1001/jama.2018.19232.

The Digital Revolution has invaded the House of Medicine, which is not really news since the invasion has been long-standing, but it seems to be generating more interest and concern in recent months. The American Medical Association recently created the Digital Health Implementation Playbook to lend guidance in developing technologies that are fundamentally altering the manner in which patients interact with health care providers.¹ The playbook lays out specific steps for developing and implementing digital health technologies such as remote patient monitoring devices. The goal of the playbook is to make certain that such devices are accurate, reliable, and validated as valuable additions to high-quality patient care.¹

In the February 2018 issue of Cutis, Masud et al² evaluated 44 patient-directed mobile applications (apps) for dermatologic conditions and developed a schematic for evaluating their value in providing valid usable information for patients. They found that most of the apps failed to live up to their purported usefulness in patient education.² I am certain we have all seen numerous examples on the Internet, many times brought to us by patients, of fallacious and inaccurate information about the diagnosis and treatment of dermatologic conditions that are actually harmful to the care of our patients.

A more upsetting trend in recent years is the proliferation of open-access journals. Although such digital journals can result in more rapid dissemination of valid scientific information, many of them do not follow a true peer-review process. So-called predatory journals from for-profit unethical publishers are increasing at an alarming rate.³

Furthermore, there is a need to present data more accurately and in formats that provide more meaningful interpretation, according to a recent Letter From the Editor in the Journal of the American Academy of Dermatology.⁴ Elston⁴ wrote: “Be honest about your data and the limitations of the study design.” He cautioned further about the proper use of statistical analysis.

As dermatologists, how do we make certain that the Digital Revolution results in better care of our patients? The answer, of course, is in education of the practitioner and our young colleagues in training. Although most Cutis readers still access the print version of our journal, more and more readers are accessing our digital format. Online we are able to offer readers the peer-reviewed content you have known to trust and rely on to improve your care of patients as well as other educational tools. Furthermore, we can provide readers access to additional charts and tables pertaining to research published in the print journal.

In January 2019 the Cutis website will merge with Dermatology News, our sister news publication, to become MDedge Dermatology (www.mdedge.com/dermatology). This site will be your new one-stop destination for timely news and clinical content you can trust from both publications. This interactive site is designed to help clinicians quickly find the information they need to improve the treatment and care of patients with conditions affecting the hair, skin, and nails. You will have free access to digital resources such as procedural videos, podcasts, image quizzes, board review, and resident resources, as well as an archive of Cutis content dating back to 2000.

As we at Cutis broaden our digital footprint, we look forward to providing our readers with a larger volume of clinically relevant content in more easily accessed formats while maintaining our commitment to valid trustworthy information. In the coming months we look forward to joining with you in this new digital endeavor, and as always, we appreciate the input of our readers during this process.

The Digital Revolution has invaded the House of Medicine, which is not really news since the invasion has been long-standing, but it seems to be generating more interest and concern in recent months. The American Medical Association recently created the Digital Health Implementation Playbook to lend guidance in developing technologies that are fundamentally altering the manner in which patients interact with health care providers.¹ The playbook lays out specific steps for developing and implementing digital health technologies such as remote patient monitoring devices. The goal of the playbook is to make certain that such devices are accurate, reliable, and validated as valuable additions to high-quality patient care.¹

In the February 2018 issue of Cutis, Masud et al² evaluated 44 patient-directed mobile applications (apps) for dermatologic conditions and developed a schematic for evaluating their value in providing valid usable information for patients. They found that most of the apps failed to live up to their purported usefulness in patient education.² I am certain we have all seen numerous examples on the Internet, many times brought to us by patients, of fallacious and inaccurate information about the diagnosis and treatment of dermatologic conditions that are actually harmful to the care of our patients.

A more upsetting trend in recent years is the proliferation of open-access journals. Although such digital journals can result in more rapid dissemination of valid scientific information, many of them do not follow a true peer-review process. So-called predatory journals from for-profit unethical publishers are increasing at an alarming rate.³

Furthermore, there is a need to present data more accurately and in formats that provide more meaningful interpretation, according to a recent Letter From the Editor in the Journal of the American Academy of Dermatology.⁴ Elston⁴ wrote: “Be honest about your data and the limitations of the study design.” He cautioned further about the proper use of statistical analysis.

As dermatologists, how do we make certain that the Digital Revolution results in better care of our patients? The answer, of course, is in education of the practitioner and our young colleagues in training. Although most Cutis readers still access the print version of our journal, more and more readers are accessing our digital format. Online we are able to offer readers the peer-reviewed content you have known to trust and rely on to improve your care of patients as well as other educational tools. Furthermore, we can provide readers access to additional charts and tables pertaining to research published in the print journal.

In January 2019 the Cutis website will merge with Dermatology News, our sister news publication, to become MDedge Dermatology (www.mdedge.com/dermatology). This site will be your new one-stop destination for timely news and clinical content you can trust from both publications. This interactive site is designed to help clinicians quickly find the information they need to improve the treatment and care of patients with conditions affecting the hair, skin, and nails. You will have free access to digital resources such as procedural videos, podcasts, image quizzes, board review, and resident resources, as well as an archive of Cutis content dating back to 2000.

As we at Cutis broaden our digital footprint, we look forward to providing our readers with a larger volume of clinically relevant content in more easily accessed formats while maintaining our commitment to valid trustworthy information. In the coming months we look forward to joining with you in this new digital endeavor, and as always, we appreciate the input of our readers during this process.

The Digital Revolution has invaded the House of Medicine, which is not really news since the invasion has been long-standing, but it seems to be generating more interest and concern in recent months. The American Medical Association recently created the Digital Health Implementation Playbook to lend guidance in developing technologies that are fundamentally altering the manner in which patients interact with health care providers.¹ The playbook lays out specific steps for developing and implementing digital health technologies such as remote patient monitoring devices. The goal of the playbook is to make certain that such devices are accurate, reliable, and validated as valuable additions to high-quality patient care.¹

In the February 2018 issue of Cutis, Masud et al² evaluated 44 patient-directed mobile applications (apps) for dermatologic conditions and developed a schematic for evaluating their value in providing valid usable information for patients. They found that most of the apps failed to live up to their purported usefulness in patient education.² I am certain we have all seen numerous examples on the Internet, many times brought to us by patients, of fallacious and inaccurate information about the diagnosis and treatment of dermatologic conditions that are actually harmful to the care of our patients.

A more upsetting trend in recent years is the proliferation of open-access journals. Although such digital journals can result in more rapid dissemination of valid scientific information, many of them do not follow a true peer-review process. So-called predatory journals from for-profit unethical publishers are increasing at an alarming rate.³

Furthermore, there is a need to present data more accurately and in formats that provide more meaningful interpretation, according to a recent Letter From the Editor in the Journal of the American Academy of Dermatology.⁴ Elston⁴ wrote: “Be honest about your data and the limitations of the study design.” He cautioned further about the proper use of statistical analysis.

As dermatologists, how do we make certain that the Digital Revolution results in better care of our patients? The answer, of course, is in education of the practitioner and our young colleagues in training. Although most Cutis readers still access the print version of our journal, more and more readers are accessing our digital format. Online we are able to offer readers the peer-reviewed content you have known to trust and rely on to improve your care of patients as well as other educational tools. Furthermore, we can provide readers access to additional charts and tables pertaining to research published in the print journal.

In January 2019 the Cutis website will merge with Dermatology News, our sister news publication, to become MDedge Dermatology (www.mdedge.com/dermatology). This site will be your new one-stop destination for timely news and clinical content you can trust from both publications. This interactive site is designed to help clinicians quickly find the information they need to improve the treatment and care of patients with conditions affecting the hair, skin, and nails. You will have free access to digital resources such as procedural videos, podcasts, image quizzes, board review, and resident resources, as well as an archive of Cutis content dating back to 2000.

As we at Cutis broaden our digital footprint, we look forward to providing our readers with a larger volume of clinically relevant content in more easily accessed formats while maintaining our commitment to valid trustworthy information. In the coming months we look forward to joining with you in this new digital endeavor, and as always, we appreciate the input of our readers during this process.

This month’s issue is packed with important science – nice to get back to medicine and not focus on politics. On page one, we highlight important new clinical guidance on the use of thiopurines in inflammatory bowel disease. This clinical practice update has some very specific and clear recommendations about thiopurines, especially in combination with biologic agents. As any clinician knowns, treatment of IBD has become complex from both a biologic standpoint and because we now recognize the importance of social determinants of health in our management of chronic diseases. We have seen an enormous outpouring of work that helps gastroenterologists develop multidisciplinary “homes” for IBD patients. These programs are now becoming best practice standards. Such approaches are practical for both academic and community GI practices. Best practice for our IBD patients now involves following clinical guidelines, understanding the impact of IBD on patients’ social and behavioral health and the incorporation of support services (or referral), and outcomes measurement. This clinical practice update will help us enhance our medical therapy for patients with both Crohn’s disease and ulcerative colitis.

Other stories include a review of the new AGA clinical practice update on endoscopic submucosal dissection for early stage cancers with important information about technique, indications, and management of complications. Questions about our approach to prevention of GI bleeding for patients in the ICU are raised by a new multicentered trial of PPI use in over 3,500 patients. Essentially, PPI prophylaxis should be reserved for seriously ill patients at high risk for bleeding – prophylaxis may not be needed in other ICU patients. Finally, another study does not support use of probiotics (at least in the current formulation) in children with gastroenteritis.

I hope you enjoy the issue and that you had a wonderful year’s end. We look forward to more excitement in 2019.

John I. Allen, MD, MBA, AGAF
Editor in Chief

This month’s issue is packed with important science – nice to get back to medicine and not focus on politics. On page one, we highlight important new clinical guidance on the use of thiopurines in inflammatory bowel disease. This clinical practice update has some very specific and clear recommendations about thiopurines, especially in combination with biologic agents. As any clinician knowns, treatment of IBD has become complex from both a biologic standpoint and because we now recognize the importance of social determinants of health in our management of chronic diseases. We have seen an enormous outpouring of work that helps gastroenterologists develop multidisciplinary “homes” for IBD patients. These programs are now becoming best practice standards. Such approaches are practical for both academic and community GI practices. Best practice for our IBD patients now involves following clinical guidelines, understanding the impact of IBD on patients’ social and behavioral health and the incorporation of support services (or referral), and outcomes measurement. This clinical practice update will help us enhance our medical therapy for patients with both Crohn’s disease and ulcerative colitis.

Other stories include a review of the new AGA clinical practice update on endoscopic submucosal dissection for early stage cancers with important information about technique, indications, and management of complications. Questions about our approach to prevention of GI bleeding for patients in the ICU are raised by a new multicentered trial of PPI use in over 3,500 patients. Essentially, PPI prophylaxis should be reserved for seriously ill patients at high risk for bleeding – prophylaxis may not be needed in other ICU patients. Finally, another study does not support use of probiotics (at least in the current formulation) in children with gastroenteritis.

I hope you enjoy the issue and that you had a wonderful year’s end. We look forward to more excitement in 2019.

John I. Allen, MD, MBA, AGAF
Editor in Chief

This month’s issue is packed with important science – nice to get back to medicine and not focus on politics. On page one, we highlight important new clinical guidance on the use of thiopurines in inflammatory bowel disease. This clinical practice update has some very specific and clear recommendations about thiopurines, especially in combination with biologic agents. As any clinician knowns, treatment of IBD has become complex from both a biologic standpoint and because we now recognize the importance of social determinants of health in our management of chronic diseases. We have seen an enormous outpouring of work that helps gastroenterologists develop multidisciplinary “homes” for IBD patients. These programs are now becoming best practice standards. Such approaches are practical for both academic and community GI practices. Best practice for our IBD patients now involves following clinical guidelines, understanding the impact of IBD on patients’ social and behavioral health and the incorporation of support services (or referral), and outcomes measurement. This clinical practice update will help us enhance our medical therapy for patients with both Crohn’s disease and ulcerative colitis.

Other stories include a review of the new AGA clinical practice update on endoscopic submucosal dissection for early stage cancers with important information about technique, indications, and management of complications. Questions about our approach to prevention of GI bleeding for patients in the ICU are raised by a new multicentered trial of PPI use in over 3,500 patients. Essentially, PPI prophylaxis should be reserved for seriously ill patients at high risk for bleeding – prophylaxis may not be needed in other ICU patients. Finally, another study does not support use of probiotics (at least in the current formulation) in children with gastroenteritis.

I hope you enjoy the issue and that you had a wonderful year’s end. We look forward to more excitement in 2019.

John I. Allen, MD, MBA, AGAF
Editor in Chief